85 results on '"CASTOLDI GL"'
Search Results
2. Preferential expression of the transcription coactivator HTIF1α gene in acute myeloid leukemia and MDS-related AML
- Author
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Gandini, D, De Angeli, C, Aguiari, G, Manzati, E, Lanza, F, Pandolfi, PP, Cuneo, A, Castoldi, GL, and del Senno, L
- Published
- 2002
- Full Text
- View/download PDF
3. The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia – analysis of 848 patients
- Author
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Visani, G, Bernasconi, P, Boni, M, Castoldi, GL, Ciolli, S, Clavio, M, Cox, MC, Cuneo, A, Del Poeta, G, Dini, D, Falzetti, D, Fanin, R, Gobbi, M, Isidori, A, Leoni, F, Liso, V, Malagola, M, Martinelli, G, Mecucci, C, Piccaluga, PP, Petti, MC, Rondelli, R, Russo, D, Sessarego, M, Specchia, G, Testoni, N, Torelli, G, Mandelli, F, and Tura, S
- Published
- 2001
- Full Text
- View/download PDF
4. Significato dell'analisi citogenetica e citogenetico-molecolare nella diagnosi e nella prognosi delle neoplasie ematologiche. Cytogenetics and molecular cytogenetics in diagnosis and prognosis of haematological malignancies
- Author
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Ciccone, Maria, Cavazzini, Francesco, and Castoldi, Gl
- Subjects
cytogenetics FISH hematologic malignancies - Published
- 2006
5. Short term treatment with Escherichia coli recombinant human granulocyte-macrophage-colony stimulating factor prior to chemotherapy for Hodgkin disease
- Author
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Aglietta, M, Montemurro, F, Fagioli, F, Volta, C, Botto, B, Cantonetti, M, Racanelli, V, Teofili, L, Amadori, S, Castoldi, Gl, Dammacco, F, Levis, A, and Ferrara, R
- Subjects
granulocyte-macrophage-colony stimulating factor ,procarbazine ,Hodgkin disease ,hybrid mechlorethamine ,vincristine, procarbazine, and prednisone ,doxorubicin, bleomycin, vinblastine, and dacarbazine ,myeloprotection ,bleomycin ,vinblastine ,and prednisone ,vincristine ,doxorubicin ,and dacarbazine - Published
- 2000
6. For the European Group for the Immunologic Classification of Leukemias (EGIL). The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias
- Author
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Bene, Mc, Bernier, M, Casasnovas, Ro, Castoldi, Gl, Knapp, W, and Lanza, F
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C-Kit ,Acute Myeloid Leukemia ,Diagnosis ,C-Kit, Diagnosis, Acute Myeloid Leukemia ,NO - Published
- 1998
7. Comparative analysis of different permeabilization methods for the flow cytometry measurement of cytoplasmic MPO and lysozyme in normal and leukemic cells
- Author
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Lanza, F, Latorraca, A, Moretti, S, Castagnari, B, Ferrari, L, and Castoldi, Gl
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myeloperoxidase ,lysozyme ,fixation reagents ,Fix and Perm ,blood cells ,acute leukemias ,FAB classification ,NO - Published
- 1997
8. Moving towards the definition of new clusters of designation at the 6th International Workshop on Leukocyte Differentiation Antigens
- Author
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Lanza, F, Moretti, S, Latorraca, A, Papa, S, Castoldi, Gl, and Shaw, S
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Human Leukocyte Differentiation Antigens ,Clustered Molecules ,Human Leukocyte Differentiation Antigens, Clustered Molecules ,NO - Published
- 1996
9. Immunophenotype definition of the stem/ progenitor cell compartment. Implications for the identification of blast cells in acute leukemia
- Author
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Moretti, S, Lanza, F, Castagnari, B, Latorraca, A, Ferrari, L, and Castoldi, Gl
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Acute Myeloid Leukemia ,Stem Cell ,growth factors ,clonogenic assays ,Stem Cell, phenotypic markers, CD34, clonogenic assays, growth factors, Acute Myeloid Leukemia ,CD34 ,phenotypic markers ,NO - Published
- 1996
10. Report on the fifth International Workshop on Human Leukocyte Differentiation Antigens
- Author
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Lanza, F, Moretti, S, Papa, S, Malavasi, F, and Castoldi, Gl
- Subjects
LEUKOCYTE DIFFERENTIATION ANIGENS ,LEUKOCYTE DIFFERENTIATION ANIGENS , MEETING REPORT, CLUSTER OF DIFFERENTIATION, NOVEL MOLECULES, FUNCTION ,NOVEL MOLECULES ,FUNCTION ,CLUSTER OF DIFFERENTIATION ,MEETING REPORT ,NO - Published
- 1994
11. Immunophenotypic and genotypic characterization of chronic lymphocytic leukemia patients from northern Italy
- Author
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Gandini, D, Lanza, F, Latorraca, A, Levato, F, Castoldi, Gl, and del Senno, L
- Subjects
mmunoglobulin (Ig) gene expression and rearrangements ,B-lymphocytes ,chronic lymphocytic leukemia ,clonality ,chronic lymphocytic leukemia, B-lymphocytes,mmunoglobulin (Ig) gene expression and rearrangements, prognosis, clonality ,prognosis ,NO - Published
- 1993
12. Reduced expression of macrophage-associated antigens on alveolar mononuclear phagocytes from AIDS patients
- Author
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Lanza, F, Ferrari, L, Sighinolfi, L, Ghinelli, F, Latorraca, A, Moretti, S, Trevisani, L, Potena, A, Malavasi, F, and Castoldi, Gl
- Subjects
pulmonary infections ,acquired immonedeficiency syndrome, alveolar macrophages, antigenic determinants, pulmonary infections ,acquired immonedeficiency syndrome ,antigenic determinants ,alveolar macrophages ,NO - Published
- 1993
13. Functional and immunophenotypic characteristics of isolated CD105 + and fibroblast + stromal cells from AML: implications for their plasticity along endothelial lineage.
- Author
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Campioni, D, Lanza, F, Moretti, S, Dominici, M, Punturieri, M, Pauli, S, Hofmann, T, Horwitz, E, and Castoldi, Gl
- Subjects
FIBROBLASTS ,CELLS ,BIOLOGY ,BONE marrow ,CYTOMETRY - Abstract
Background In vitro cultures of BM cells from newly diagnosed patients with AML displayed a defective BM stromal compartment, with a reduced number of fibroblast-colony-forming unit (CFU-F: 1±1.25 SD) and a decreased proliferative ability. The purposes of our study were: 1) to select BM mesenchymal stem cells (MSC) and BM-derived stromal cells (BMDSCs) from AML patients at diagnosis and from healthy subjects, using an immunomagnetic system and either anti-CD105 or anti-fibroblast MAbs; 2) to study the immunophenotypic and functional properties of freshly isolated and cultured mesenchymal cells; 3) to test the in vitro plasticity of the selected cells to differentiate towards an endothelial phenotype. Methods Fresh mononuclear cells obtained from BM of 20 patients newly diagnosed with AML and from eight healthy subjects were selected by using anti-fibroblast and anti-CD105 MAbs. Freshly isolated cells were analyzed, characterized by flow cytometry using a wide panel of MAbs and seeded in long-term culture medium to assess CFU-F formation. The level of confluence after 30 days and functional capacity in a long-term colony-forming cell culture (LTC-CFC) were tested. Furthermore, the cultured selected cell populations were assayed for their ability to differentiate into an endothelial-like cell phenotype with the addition of vascular endothelial growth factor (VEGF) and endothelial cell growth supplement (ECGS). Results In normal subjects the selection produced an increase of the CFU-F number of 2.6-fold with anti-fibroblast MAb and 2.7-fold with the anti-CD105 MAb. Anti-fibroblast and anti-CD105 MAb selection from AML BM cells resulted in a statistically significant greater count of CFU-F that was respectively 10.6-fold (P=0.04) and 14.4-fold (P=0.00001) higher in comparison with the unselected AML samples. Interestingly, in 80% of AML samples immunoselection was also able to restore the capacity of the CFU-F to proliferate and form confluent stromal layers. The isolation of those layers sustained the proliferation and differentiation of hematopoietic stem cells in the LTC-CFC. The phenotypic profile of cultured BMDSCs was different from that of the freshly isolated cells, and changed in relation to the culture conditions: CD105 + selected cells cultured with VEGF and ECGS expressed endothelial markers, a finding that suggests that this cell subpopulation may have the potential to differentiate toward an endothelial-like phenotype. Discussion We report that immunomagnetic selection represents a valid tool for the selection of BM mesenchymal cells in samples obtained from both healthy subjects and patients with AML. This technique was able to rescue two functional and immunophenotypic compartments related to two different selected populations. In particular, the CD105 + cells isolated in AML displayed, after stimulation with VEGF and ECGS, the ability to change towards an endothelial-like cell phenotype, thus revealing an unexpected plasticity. Both CD105 + and fibroblast + cells once successfully isolated might represent sources of mesenchymal cells populations useful for in vitro investigations and, above all, as therapeutic devices. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
14. Exercise capacity and circulating endothelial progenitor cells in hemodialysis patients.
- Author
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Manfredini F, Rigolin GM, Malagoni AM, Soffritti S, Boari B, Conconi F, Castoldi GL, Catizone L, Zamboni P, and Manfredini R
- Subjects
- Aged, Antigens, CD34, Cell Count, Exercise Test, Female, Humans, Kidney Failure, Chronic therapy, Male, Middle Aged, Endothelial Cells physiology, Exercise Tolerance physiology, Kidney Failure, Chronic physiopathology, Renal Dialysis, Stem Cells physiology
- Abstract
Mobilization of circulating endothelial progenitor cells (EPCs) is increased after acute exercise and training. This study aims to evaluate whether, in a low performance population, EPC levels may be related to exercise capacity in steady state conditions. Study population consisted of sixteen hemodialysis patients. The distance walked in the 6-minute walking test (6 MWD) and the maximal speed attained in an incremental treadmill test were used to assess the exercise capacity. Physical functioning was measured by the scale on the SF36 questionnaire. Quantification of peripheral blood CD34(+) cells and enumeration of EPCs, assessed as CD34(+) cells coexpressing AC 133 and vascular endothelial growth factor receptor-2, were performed. Hemoglobin concentration, white blood cells, high-sensitivity C-reactive protein, total cholesterol, and triglycerides were measured. Statistical analysis examined the relationship between blood progenitors cells versus performance parameters, laboratory parameters, age, body mass index, hemodialysis duration, and erythropoietin therapy. Univariate analysis revealed a significant association between percentage values of EPC and performance parameters only: 6 MWD (r=0.720; p=0.0017), maximal treadmill speed (r=0.721; p=0.0016), and physical functioning score (r=0.506; p=0.0453). A similar statistical association between EPC absolute values and performance parameters was found. No correlation between CD34 (+) and any parameter under study was observed. Multivariate analysis indicated 6 MWD as the most significant independent factor associated with EPC level. EPC percentage value was significantly lower (p=0.0087) in the worse (6 MWD < 300 m, n=8) than in the better performing group (6 MWD > 300 m, n=8). In a group of renal patients, mobilization of EPCs was related to the degree of exercise capacity, suggesting a possible connection with the cardiovascular risk in low performance populations limited by chronic diseases.
- Published
- 2007
- Full Text
- View/download PDF
15. Immunophenotypic heterogeneity of bone marrow-derived mesenchymal stromal cells from patients with hematologic disorders: correlation with bone marrow microenvironment.
- Author
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Campioni D, Moretti S, Ferrari L, Punturieri M, Castoldi GL, and Lanza F
- Subjects
- Adult, Aged, Cells, Cultured, Humans, Middle Aged, Stromal Cells immunology, Bone Marrow Cells immunology, Environment, Hematologic Diseases genetics, Hematologic Diseases immunology, Immunophenotyping
- Abstract
The immunophenotypic analysis of ex vivo-expanded mesenchymal stromal cells (MSC) has so far been confined to single or dual staining analysis in normal subjects. In this study, using a four-color cytofluorimetric protocol, we demonstrated that cultured MSC derived from the bone marrow of patients with hematologic malignancies showed alterations in the expression of CD105, CD90, CD184, and HLA-DR molecules. The decrease in the percentage of CD105+ and CD90+ MSC correlated with an increased bone marrow angiogenesis. This paper provides evidence that multiparametric flow cytometry is essential for the establishment of a standardized protocol to identify various MSCs subsets and aberrant phenotypes.
- Published
- 2006
16. Functional and immunophenotypic characteristics of isolated CD105(+) and fibroblast(+) stromal cells from AML: implications for their plasticity along endothelial lineage.
- Author
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Campioni D, Lanza F, Moretti S, Dominici M, Punturieri M, Pauli S, Hofmann T, Horwitz E, and Castoldi GL
- Subjects
- Adult, Amyotrophic Lateral Sclerosis immunology, Antigens, CD, Endoglin, Endothelium physiology, Female, Fibroblasts immunology, Humans, Immunomagnetic Separation, Male, Middle Aged, Receptors, Cell Surface, Stromal Cells immunology, Vascular Cell Adhesion Molecule-1 immunology, Amyotrophic Lateral Sclerosis physiopathology, Fibroblasts physiology, Stromal Cells physiology, Vascular Cell Adhesion Molecule-1 physiology
- Abstract
Background: In vitro cultures of BM cells from newly diagnosed patients with AML displayed a defective BM stromal compartment, with a reduced number of fibroblast-colony-forming unit (CFU-F: 1 +/- 1.25 SD) and a decreased proliferative ability. The purposes of our study were: 1). to select BM mesenchymal stem cells (MSC) and BM-derived stromal cells (BMDSCs) from AML patients at diagnosis and from healthy subjects, using an immunomagnetic system and either anti-CD105 or anti-fibroblast MAbs; 2). to study the immunophenotypic and functional properties of freshly isolated and cultured mesenchymal cells; 3). to test the in vitro plasticity of the selected cells to differentiate towards an endothelial phenotype., Methods: Fresh mononuclear cells obtained from BM of 20 patients newly diagnosed with AML and from eight healthy subjects were selected by using anti-fibroblast and anti-CD105 MAbs. Freshly isolated cells were analyzed, characterized by flow cytometry using a wide panel of MAbs and seeded in long-term culture medium to assess CFU-F formation. The level of confluence after 30 days and functional capacity in a long-term colony-forming cell culture (LTC-CFC) were tested. Furthermore, the cultured selected cell populations were assayed for their ability to differentiate into an endothelial-like cell phenotype with the addition of vascular endothelial growth factor (VEFG) and endothelial cell growth supplement (ECGS)., Results: In normal subjects the selection produced an increase of the CFU-F number of 2.6-fold with anti-fibroblast MAb and 2.7-fold with the anti-CD105 MAb. Anti-fibroblast and anti-CD105 MAb selection from AML BM cells resulted in a statistically significant greater count of CFU-F that was respectively 10.6-fold (P = 0.04) and 14.4-fold (P = 0.00001) higher in comparison with the unselected AML samples. Interestingly, in 80% of AML samples immunoselection was also able to restore the capacity of the CFU-F to proliferate and form confluent stromal layers. The isolation of those layers sustained the proliferation and differentiation of hematopoietic stem cells in the LTC-CFC. The phenotypic profile of cultured BMDSCs was different from that of the freshly isolated cells, and changed in relation to the culture conditions: CD105+ selected cells cultured with VEGF and ECGS expressed endothelial markers, a finding that suggests that this cell subpopulation may have the potential to differentiate toward an endothelial-like phenotype., Discussion: We report that immunomagnetic selection represents a valid tool for the selection of BM mesenchymal cells in samples obtained from both healthy subjects and patients with AML. This technique was able to rescue two functional and immunophenotypic compartments related to two different selected populations. In particular, the CD105+ cells isolated in AML displayed, after stimulation with VEGF and ECGS, the ability to change towards an endothelial-like cell phenotype, thus revealing an unexpected plasticity. Both CD105+ and fibroblast+ cells once successfully isolated might represent sources of mesenchymal cells populations useful for in vitro investigations and, above all, as therapeutic devices.
- Published
- 2003
- Full Text
- View/download PDF
17. Comparison of single and dual platform methodologies for the estimation of CD34+ hematopoietic progenitor cells: correlation with colony assay.
- Author
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Moretti S, Dabusti M, Castagnari B, Tieghi A, Ferrari L, Campioni D, Punturieri M, Dominici M, Castoldi GL, and Lanza F
- Subjects
- Adolescent, Adult, Fetal Blood cytology, Humans, Middle Aged, Antigens, CD34 blood, Blood Cell Count methods, Flow Cytometry methods, Hematopoietic Stem Cells
- Abstract
In this study three assays for the enumeration of CD34+ progenitors were compared: 1) a modified version of the Milan protocol, used in the standard dual-platform format; 2) a dual-platform version of the ISHAGE protocol; 3) the ProCOUNT software version 2.0/ProCOUNT kit. The assays were compared to validate the accuracy of CD34+ cell counts in mobilized peripheral blood (PB), apheresis products (AP), and cord blood (CB). The ProCOUNT protocol uses reference beads for absolute CD34+ cell counting, whereas CD34 counts by other techniques are derived from a separate leukocyte count performed by a hematology analyzer. A good correlation between the ISHAGE and ProCOUNT methods was obtained for estimation of CD34+ counts in PB (n=42 samples analyzed) and AP (n=35)--except for samples having a leukocyte count >25 x 10(9)/L or a CD34 count <0.0025 x 10(9)/L)--while a suboptimal correlation between the methods was observed for CB (n=30). The ProCOUNT system proved to be effective in reducing the variability in CD34+ cell counting and appeared to be useful for intralaboratory methodology standardization. The main disadvantage of the ProCOUNT assay was its inability to calculate CD34 counts in leukopenic samples and in CB samples showing a high erythroblast count. As far as the correlation with hematopoietic colonies is concerned, data collected from apheresis samples showed a good correlation between the three flow cytometry methods and colony-forming unit granulocyte-macrophage (CFU-GM) counts, confirming the value of the flow cytometric test as a real-time, truly predictive test to measure the hematopoietic potential of the graft. In summary, all methods are suitable for enumeration of most PB samples, while the single-platform methodology should be preferred for the analysis of AP and CB. We also found the dual-platform format of the ISHAGE method precise and accurate for the estimation of CD34+ cells from CB samples. Based on these data it can be concluded that the single-platform flow cytometry assay format should be the preferred approach for CD34+ stem cell enumeration in different types of samples.
- Published
- 2002
- Full Text
- View/download PDF
18. BCR-ABL rearrangement is not detectable in essential thrombocythemia.
- Author
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Emilia G, Marasca R, Zucchini P, Temperani P, Luppi M, Torelli G, Lanza F, De Angelis C, Gandini D, Castoldi GL, Vallisa D, Cavanna L, and del Senno L
- Subjects
- Acute Disease, Adult, Aged, Aged, 80 and over, Female, Humans, Italy epidemiology, Leukemia, Myeloid genetics, Male, Middle Aged, Philadelphia Chromosome, Reverse Transcriptase Polymerase Chain Reaction, Sensitivity and Specificity, Thrombocythemia, Essential blood, Thrombocythemia, Essential epidemiology, Fusion Proteins, bcr-abl genetics, Thrombocythemia, Essential genetics
- Published
- 2001
- Full Text
- View/download PDF
19. Detection of BCR/ABL rearrangements in adult acute lymphoblastic leukemia using a highly sensitive interphase fluorescence in situ hybridization method (D-FISH).
- Author
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Mancini M, Nanni M, Sirleto P, De Cuia MR, Castoldi GL, Cilloni D, Cimino G, Mecucci C, Pane F, Annino L, Di Raimondo F, Santoro A, Specchia G, Tedeschi A, Todeschini G, and Foá R
- Subjects
- Adolescent, Adult, Cytogenetic Analysis, Female, Fusion Proteins, bcr-abl analysis, Gene Rearrangement genetics, Humans, In Situ Hybridization, Fluorescence standards, Interphase, Male, Middle Aged, Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Prospective Studies, Reproducibility of Results, Reverse Transcriptase Polymerase Chain Reaction, Sensitivity and Specificity, Fusion Proteins, bcr-abl genetics, In Situ Hybridization, Fluorescence methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Translocation, Genetic genetics
- Abstract
Introduction: One hundred-and-six adult cases of acute lymphoblastic leukemia were prospectively investigated using a highly sensitive interphase fluorescence in situ hybridization assay which utilizes DNA probes that detect a double BCR/ABL fusion signal (D-FISH) in cells carrying the t(9;22) to evaluate the reliability and specificity of this method for the detection of the Ph translocation. The results were compared with those obtained in the same cases by conventional cytogenetics and by reverse-transcription polymerase chain reaction., Materials and Methods: The study was performed using DNA probes that span the common breakpoints of the t(9;22) translocation and that detect a double BCR/ABL fusion in cells carrying this karyotypic anomaly, one on the abnormal chromosome 9 and one on the Ph chromosome., Results: Interphase D-FISH detected a high number of rearranged cases (22/106) compared to conventional cytogenetics (15/106) and RT-PCR (21/106)., Conclusion: Interphase D-FISH emerges as a reliable, fast and relatively inexpensive tool for the detection of BCR/ABL rearrangements in adult ALL patients at diagnosis. It has a sensitivity clearly higher than conventional karyotyping and it may prove also superior to that of RT-PCR in cases with unusual BCR/ABL breakpoints. Our results suggest that D-FISH might be considered as the initial test for the diagnosis of Ph+ adult ALL.
- Published
- 2001
- Full Text
- View/download PDF
20. CD123 (interleukin 3 receptor alpha chain).
- Author
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Moretti S, Lanza F, Dabusti M, Tieghi A, Campioni D, Dominici M, and Castoldi GL
- Subjects
- Amino Acid Sequence, Animals, Antibodies, Monoclonal immunology, Chromosome Mapping, Humans, Interleukin-3 Receptor alpha Subunit, Mice, Molecular Sequence Data, Phenotype, Receptors, Interleukin-3 chemistry, Receptors, Interleukin-3 physiology, Receptors, Interleukin-3 analysis
- Published
- 2001
21. BCL-1 rearrangements and p53 mutations in atypical chronic lymphocytic leukemia with t(11;14)(q13;q32).
- Author
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De Angeli C, Gandini D, Cuneo A, Moretti S, Bigoni R, Roberti MG, Bardi A, Castoldi GL, and del Senno L
- Subjects
- Adult, Aged, B-Lymphocytes immunology, B-Lymphocytes metabolism, Cytogenetic Analysis, Female, Gene Rearrangement, Humans, Immunophenotyping, Lymphoma, Mantle-Cell genetics, Male, Middle Aged, Multiple Myeloma genetics, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 14, Genes, bcl-1, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Mutation, Translocation, Genetic, Tumor Suppressor Protein p53 genetics
- Abstract
Background and Objectives: The translocation t(11;14) (q13;q32), typically described in mantle cell lymphomas (MCL), has also been found in some cases of non-MCL lymphoproliferative disorders, such as splenic lymphoma with villous lymphocytes (SLVL), multiple myeloma (MM), prolymphocytic leukemia (PLL), typical and atypical chronic lymphocytic leukemia (CLL and aCLL). In order to define better the genetic features of aCLL with t(11;14), which could represent a distinct disease subset, we looked for genetic lesions in the BCL-1 locus and in BCL-2, BCL-6, c-myc and p53 genes., Design and Methods: We investigated a panel of B-lymphoproliferative disorders with translocation t(11;14)(q13;q32) including nine aCLL, six MCL and one MM. Southern and Northern blot analysis was used to investigate DNA structure and RNA expression; SSCP and direct sequencing were used to detect and characterize p53 point mutations; cytofluorimetric analysis was used to quantify p53 protein., Results: Alterations of BCL-2, BCL-6 and c-myc were not detected. Conversely, BCL-1 rearrangements were present in 4 out of 7 aCLL and in 2 out of 4 MCL. A high incidence of p53 gene alterations was found, almost equivalent in aCLL and MCL., Interpretation and Conclusions: Our results indicate that the occurrence of BCL-1 locus lesions in aCLL selected for t(11;14) is as high as in MCL. Interestingly, rearrangements in the mTC1 (minor translocation cluster 1) were only found in aCLL. Therefore, the two B-cell chronic lymphoproliferative disorders share similar molecular rearrangements and the t(11;14) identifies a subset of B-CLL sharing molecular features with MCL and characterized by aggressive clinical evolution.
- Published
- 2000
22. Short term treatment with Escherichia coli recombinant human granulocyte-macrophage-colony stimulating factor prior to chemotherapy for Hodgkin disease.
- Author
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Aglietta M, Montemurro F, Fagioli F, Volta C, Botto B, Cantonetti M, Racanelli V, Teofili L, Ferrara R, Amadori S, Castoldi GL, Dammacco F, and Levis A
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bleomycin administration & dosage, Bleomycin adverse effects, Combined Modality Therapy, Dacarbazine administration & dosage, Dacarbazine adverse effects, Dose-Response Relationship, Drug, Double-Blind Method, Doxorubicin administration & dosage, Doxorubicin adverse effects, Female, Granulocyte-Macrophage Colony-Stimulating Factor pharmacology, Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use, Humans, Injections, Subcutaneous, Male, Mechlorethamine administration & dosage, Mechlorethamine adverse effects, Middle Aged, Prednisone administration & dosage, Prednisone adverse effects, Procarbazine administration & dosage, Procarbazine adverse effects, Prospective Studies, Recombinant Proteins, Vinblastine administration & dosage, Vinblastine adverse effects, Vincristine administration & dosage, Vincristine adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Granulocyte-Macrophage Colony-Stimulating Factor administration & dosage, Hodgkin Disease drug therapy, Neutropenia prevention & control
- Abstract
Background: Granulocyte-macrophage-colony stimulating factor (GM-CSF) administration stimulates the proliferation of hemopoietic progenitors. Shortly (48-96 hours) after its discontinuation, feedback phenomena occur and the progenitor proliferation rate drops below baseline levels. As the quiescence of hyperplastic bone marrow suggests that hemopoietic cells may be refractory to the toxic effects of cytostatic drugs, the decision was made to test the hypothesis that GM-CSF given before chemotherapy may be myeloprotective., Methods: Fifty-six patients with newly diagnosed Stage II-IV Hodgkin disease, ages 18-77 years, were randomized to receive GM-CSF (5 microg/kg subcutaneously) or placebo from Day 7 to Day 4 before each chemotherapy administration (6 cycles of a hybrid of mechlorethamine, vincristine, procarbazine, and prednisone with doxorubicin, bleomycin, vinblastine, and dacarbazine). The treatment was considered a success if the delivery rate of chemotherapy was >90% after 3 cycles and >80% after 6 cycles., Results: Thirty patients received GM-CSF and 26 placebo. The dose intensity (85.2% vs. 79.6%) and the overall success in terms of delivery rate (56.7% vs. 50%) were higher in the GM-CSF group, although these differences were not statistically significant. The neutrophil nadirs were higher in the GM-CSF group during the first three cycles and subsequently similar in both groups., Conclusions: No significant differences in terms of myelotoxicity or drug delivery were observed between the two treatment arms. Although the myeloprotective effect of the prechemotherapy administration of GM-CSF seems to be minimal, the data indicate a safe timing between GM-CSF discontinuation and further chemotherapy. Because cumulative myelotoxicity has been observed with other growth factors, given in the interval between the chemotherapy cycles, this may be relevant to the planning of rapid cycling., (Copyright 2000 American Cancer Society.)
- Published
- 2000
- Full Text
- View/download PDF
23. A novel translocation t(1;7)(p36;q34) in three patients with acute myeloid leukaemia.
- Author
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Specchia G, Cuneo A, Liso V, Contino R, Pastore D, Gentile E, Rocchi M, and Castoldi GL
- Subjects
- Adult, Female, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Male, Middle Aged, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 7 genetics, Leukemia, Myeloid, Acute genetics, Leukemia, Myelomonocytic, Acute genetics, Translocation, Genetic genetics
- Abstract
Studies of large numbers of patients have enabled the identification of relatively infrequent chromosome changes, such as inv(3)(q21;q26), t(6;9)(p23;q34) and t(8;16)(p11;p11), whose clinico-biological significance is gradually becoming clearer. Translocations involving chromosomes 1 and 7 are relatively rare in myeloid neoplasias, being found in far less than 1% of cases; the rearrangement that occurs most frequently consists of an unbalanced translocation [t(1;7)(p11; p11)], resulting in complete loss of 7q, associated with therapy-related or environmentally-induced high-risk myelodysplasia. We recently observed three cases of acute myeloid leukaemia (AML) with a previously unreported balanced translocation t(1;7) (p36;q34). Case 1 underwent autologous bone marrow transplantation and remains alive in CR; cases 2 and 3 relapsed after 10 and 4 months, respectively. The response to chemotherapy observed in our cases suggests that variable clinical features might be present in the broad cytogenetic category usually referred to as '7q abnormalities' and contributes to an interesting previous observation of prolonged disease-free survival in a subset of AMLs with 7q- as the isolated chromosome change.
- Published
- 1999
24. Expression and functional role of urokinase-type plasminogen activator receptor in normal and acute leukaemic cells.
- Author
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Lanza F, Castoldi GL, Castagnari B, Todd RF 3rd, Moretti S, Spisani S, Latorraca A, Focarile E, Roberti MG, and Traniello S
- Subjects
- Acute Disease, Female, Flow Cytometry, Hematopoietic Stem Cells metabolism, Humans, Male, Neutrophils metabolism, Receptors, Urokinase Plasminogen Activator, Leukemia metabolism, Plasminogen Activators metabolism, Receptors, Cell Surface metabolism
- Abstract
Urokinase-type plasminogen activator receptor (UPA-R-CD87) is a GPI-anchored membrane protein which promotes the generation of plasmin on the surface of many cell types, probably facilitating cellular extravasation and tissue invasion. A flow cytometric quantitative analysis of expression levels for UPA-R was performed on fresh blast cells from patients with acute myeloid leukaemia (AML, n = 74), acute lymphoblastic leukaemia (ALL, n = 24), and biphenotypic leukaemia (BAL, n = 3) using two CD87 monoclonal antibodies (McAbs) (3B10 and VIM5). Peripheral blood and bone marrow (BM) cells from 15 healthy adults served as controls. Using 3B10 McAb, UPA-R was expressed (>99%) by blood monocytes, neutrophils, and BM myelomonocytic precursors in controls, whereas resting T and B lymphocytes, and CD34+ cells were UPA-R negative. We also attempted to clarify whether UPA-R has a role in mediating neutrophil functions. Oriented locomotion induced by different chemotaxins and lysozyme release by granules stimulated with fMLP or PMA were significantly decreased when UPA-R was neutralized by CD87 McAb. In contrast, the anti-UPA-R McAb had no effect on superoxide anion generation of normal neutrophils. Blasts from AML showed a heterogenous pattern of expression for the UPA-R McAbs, with reactivity strictly dependent on FAB subtype. The highest UPA-R expression was seen in the M5 group: all patients tested (n = 20) showed strong positivity for the UPA-R McAb whereas only 12% (3/24) of ALL patients were CD87 positive, and 2/3 of BAL patients showed a dim expression for CD87. The number of receptors expressed by blast cells in 6/74 (8.1%) AML patients was higher than those of normal samples: in addition, since co-expression of UPA-R and CD34 was not found in normal haemopoietic cells, it may be postulated that CD87 can be used alone (when overexpressed) or in combination with CD34 for the detection of minimal residual disease. Results also indicated that patients with UPA-receptors >12 x 10(3) ABC/cell, irrespective of FAB subtype, had a greater tendency for cutaneous and tissue infiltration and a higher frequency of chromosome abnormalities, thus suggesting the concept that cellular UPA-R content positively correlates with the invasive potential of AML cells. The combination of higher UPA-R positivity, abnormalities of chromosome 11, and M5 FAB morphology may identify a peculiar subset of AML, characterized by a more aggressive clinical course.
- Published
- 1998
- Full Text
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25. The effectiveness and tolerability of epoetin alfa in patients with multiple myeloma refractory to chemotherapy.
- Author
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Dammacco F, Silvestris F, Castoldi GL, Grassi B, Bernasconi C, Nadali G, Perona G, De Laurenzi A, Torelli U, Ascari E, Rossi Ferrini PL, Caligaris-Cappio F, Pileri A, and Resegotti L
- Subjects
- Aged, Anemia etiology, Antineoplastic Agents therapeutic use, Blood Transfusion, Epoetin Alfa, Erythropoietin adverse effects, Female, Humans, Karnofsky Performance Status, Male, Middle Aged, Multiple Myeloma drug therapy, Recombinant Proteins, Anemia therapy, Erythropoietin therapeutic use, Multiple Myeloma complications
- Abstract
Anemia is a frequent complication of multiple myeloma, becoming chronic in patients who are resistant to chemotherapy. This randomized, parallel, controlled multicenter study (71 patients receiving concomitant chemotherapy) evaluated the efficacy and safety of epoetin alfa in improving anemia and eliminating the need for transfusions in multiple myeloma patients refractory to conventional first- or second-line chemotherapy. Forty patients were treated with subcutaneous epoetin alfa (150 IU/kg per dose, increasing to 300 IU/kg per dose, every 3 weeks) for 6 months, and 31 entered a control group. The epoetin alfa group had a significantly (P < or = 0.001) greater percentage of patients (75% vs. 21%) with increases in hemoglobin levels and/or reduced transfusion requirements. In 44 non pre-transfused patients (20 controls, 24 in the epoetin alfa group), the mean increase in hemoglobin was significantly (P < or = 0.0001) greater in the epoetin alfa group (+2.1 vs. -0.2 g/dl). Increases in hematocrit and red blood cells were also significantly (P < or = 0.0001) greater in epoetin alfa-treated patients, with corresponding reductions in transfusion requirement. In the 27 pre-transfused patients (11 controls, 16 in the epoetin alfa group), there was a trend towards reduced transfusional need in epoetin alfa-treated patients. Thus, in patients with multiple myeloma refractory to chemotherapy epoetin alfa is a well-tolerated treatment which improves anemia in non pre-transfused patients and appears to reduce transfusion need in those previously transfused.
- Published
- 1998
- Full Text
- View/download PDF
26. Expression and functional role of urokinase-type plasminogen activator receptor (UPA-R; CD87) in normal and acute leukemia cells.
- Author
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Castagnari B, Moretti S, Latorraca A, Spisani S, Traniello S, Castoldi GL, and Lanza F
- Subjects
- Acute Disease, Antigens, CD metabolism, Blood Cells metabolism, Flow Cytometry, Humans, Receptors, Cell Surface physiology, Receptors, Urokinase Plasminogen Activator, Hematopoietic Stem Cells metabolism, Leukemia, Myeloid metabolism, Leukocytes metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism, Receptors, Cell Surface metabolism
- Published
- 1997
27. Flow cytometry measurement of cytokine receptors in acute leukemias. Clinical and biologic implications.
- Author
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Lanza F, Moretti S, Castagnari B, Latorraca A, Focarile E, Ferrari L, and Castoldi GL
- Subjects
- Acute Disease, Antigens, CD metabolism, Flow Cytometry, Humans, Immunophenotyping, Leukemia, Myeloid metabolism, Myelodysplastic Syndromes metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism, Leukemia metabolism, Receptors, Cytokine metabolism
- Published
- 1997
28. Diagnostic value of MPO and lysozyme antibodies in acute leukemia. Implications for the definition of FAB subtypes using a flow cytometric approach in combination with different permeabilising methods.
- Author
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Latorraca A, Lanza F, Ferrari L, and Castoldi GL
- Subjects
- Acute Disease, Antibodies metabolism, Fluorescent Antibody Technique, Direct, Humans, Leukemia, Myeloid classification, Precursor Cell Lymphoblastic Leukemia-Lymphoma classification, Precursor Cell Lymphoblastic Leukemia-Lymphoma enzymology, Cell Membrane Permeability drug effects, Flow Cytometry methods, Leukemia, Myeloid enzymology, Muramidase immunology, Peroxidase immunology
- Published
- 1997
29. Characterization of t(11;14) translocation in mantle cell lymphoma by fluorescent in situ hybridization.
- Author
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Bigoni R, Negrini M, Veronese ML, Cuneo A, Castoldi GL, and Croce CM
- Subjects
- Aged, Chromosomes, Artificial, Yeast, Female, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 14, Lymphoma, Non-Hodgkin genetics, Translocation, Genetic
- Abstract
Characterization of chromosome abnormalities in leukemia and lymphoma have contributed to the understanding of the molecular basis of these neoplastic diseases. In addition, specific chromosomal aberrations have acquired diagnostic or prognostic value. The t(11;14)(q13;q32) chromosome translocation has been detected in mantle cell lymphomas. However, possibly due to the limits of conventional cytogenetic analysis and the presence of different breakpoints at the molecular level, it is possible that the true percentage of association is underestimated. In our study, we used a yeast artificial chromosome, spanning the entire area where the rearrangements occur on chromosome 11q13, to detect the presence of translocations by fluorescent in situ hybridization experiments. We detected BCL-1 translocations in eight of eight patients with clinical and immunological features of mantle cell lymphoma, suggesting that the t(11;14) translocation is a critical event in the pathogenesis of MCL and may be a primary element for the diagnosis. Since this translocation is associated with poor prognosis, its detection may help to make a correct diagnosis as well as to evaluate residual disease, which is critical to plan a rational chemotherapy regimen.
- Published
- 1996
30. Moving towards the definition of new clusters of designation at the 6th International Workshop on Human Leukocyte Differentiation Antigens. A brief description of the recently clustered molecules.
- Author
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Lanza F, Moretti S, Latorraca A, Papa S, Castoldi GL, and Shaw S
- Subjects
- Antigens, CD analysis, Cluster Analysis, Humans, Antigens, CD classification
- Published
- 1996
31. Immunophenotype definition of the stem/progenitor cell compartment. Implications for the identification of blast cells in acute leukemia.
- Author
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Moretti S, Lanza F, Castagnari B, Latorraca A, Ferrari L, Resca R, Renò F, Papa S, and Castoldi GL
- Subjects
- Acute Disease, Humans, Immunophenotyping, Hematopoietic Stem Cells chemistry, Hematopoietic Stem Cells pathology, Leukemia pathology
- Published
- 1996
32. Flow cytometry evaluation of urokinase-type plasminogen activator receptor (UPA-R) in acute myeloid leukemia cells.
- Author
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Castagnari B, Moretti S, Latorraca A, Rigolin GM, Balsamo R, Lanza F, and Castoldi GL
- Subjects
- Acute Disease, Flow Cytometry, Humans, Leukemia, Myeloid, Acute pathology, Neoplasm Invasiveness, Precursor Cell Lymphoblastic Leukemia-Lymphoma enzymology, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Leukemia, Myeloid, Acute enzymology, Neoplasm Proteins analysis, Neoplastic Stem Cells enzymology, Urokinase-Type Plasminogen Activator analysis
- Abstract
The aim of this study was to investigate by flow cytometry the expression of the UPA-R (Urokinase type plasminogen activator receptor-CD87) on the blastic population of AML and ALL patients in order to evaluate whether the presence of this molecule could be associated with peculiar clinical and biologic features of leukemic cells. Five different monoclonal antibodies (MoAbs) (clones: 3B10#; VIM5*; 109#; 68#; 100#) were used in order to detect the distinct forms of this cellular receptor. Cell reactivity varied significantly from case to case, also depending on the MoAb used for the flow cytometry analysis. In brief, 3B10# and VIM5* MoAbs were found to be positive in more than 90% of monocytes and neutrophils from healthy subjects, while the number of positive cells was decreased (60%) using the 109# MoAb. However, either 68# and 100# MoAbs recognised only a low number of blood monocytes and neutrophils (8-20%), while lymphocytes were unreactive with all the five UPA-R MoAbs. ALL cells were found to be CD87 negative in all cases. Blasts from AML showed a heterogeneous pattern of expression for the UPA-R MoAbs, being the reactivity strictly dependent on the MoAb used, and, to a higher extent, on the degree and type of maturation of the blastic cells. The number of blasts recognising 3B10# and VIM5* MoAbs was significantly higher than that reacting with the remaining MoAbs irrespective of the FAB subtype. Since proteolytic enzymes, like UPA, play a key role in the dissolution of the extracellular matrix, and in facilitating the cell egress from the bone marrow, it is conceivable that the expression of the UPA-R could contribute to the invasive properties and, possibly, metastatic potential of leukemic cells.
- Published
- 1995
33. Novel small deletions of the p53 gene in late-stage B-cell chronic lymphocytic leukaemia.
- Author
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Gandini D, Aguiari GL, Cuneo A, Piva R, Castoldi GL, and del Senno L
- Subjects
- Aged, Base Sequence, Female, Humans, Molecular Sequence Data, Point Mutation, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, Genes, p53 genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Sequence Deletion
- Abstract
A group of 20 CLL patients selected for advanced clinical stage p53 mutations were analysed by single-strand conformational polymorphism (SSCP) following PCR amplification of exons 5-9. In two patients abnormal SSCP of either exon 5 or exon 8 was found and PCR products were analysed by direct sequencing. A hemizygous or homozygous 12bp deletion at codon 135 and 3bp heterozygous deletion at codon 264 were detected; also, in the latter sample a heterozygous mutation at codon 282 (Arg to Gln) was found. To our knowledge, this is the first report of p53 deletions in B-CLL. The two patients were elderly, and both had a rapidly progressive disease in the absence of unfavourable cytogenic abnormalities. These findings support a role for p53 alterations in the clinical course of some B-CLL patients.
- Published
- 1994
- Full Text
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34. Acute promyelocytic leukemia: morphological aspects.
- Author
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Castoldi GL, Liso V, Specchia G, and Tomasi P
- Subjects
- Basophils pathology, Bone Marrow pathology, Carboxylic Ester Hydrolases analysis, Cytoplasm pathology, Cytoplasm ultrastructure, Cytoplasmic Granules pathology, Cytoplasmic Granules ultrastructure, Granulocytes enzymology, Granulocytes pathology, Granulocytes ultrastructure, Histocytochemistry, Humans, Leukemia, Promyelocytic, Acute enzymology, Peroxidase analysis, Leukemia, Promyelocytic, Acute pathology
- Abstract
Among AML with maturation, acute promyelocytic leukemia (APL) represents a distinct subtype which accounts for 5-10% of all the FAB variants. APL may be recognized by different cytological pictures: (i) Hypergranular APL, the most typical form, showing promyelocytes with cytoplasm packed with purple granules. Most of the primary granules may be incorporated into Auer rods, sometimes stacked in bundles of faggots. (ii) Microgranular APL, characterized by fine dustlike granulation in the cytoplasm; some promyelocytes may even appear agranular by light microscopy. Most of the cells show bilobed or folded nuclei, a picture which may simulate that of acute myelomonocytic leukemia. (iii) Hyperbasophilic form, characterized by cells with high N/C ratio, and strongly basophilic cytoplasm with either sparse or no granules. Conspicuous cytoplasmatic budding is usually present, recalling the feature of micromegakaryocytes. Strong positivity for myeloperoxidase, Sudan black B and chloroacetate esterase represents the typical cytochemical pattern of M3; usually a weaker reactivity may be observed in M3v. However, sometimes a degree of cytochemical heterogeneity of APL cells may be observed, as suggested by cases displaying a strong sodium fluoride-sensitive non-specific esterase reaction. Recently a distinct entity associated with basophilic differentiation has been described. Differential diagnosis of this form with M2-baso subtype and with cases of MDS or AML with basophilia (M2, M4 with t(6;9) translocation) may be obtained by the use of cytochemistry, cytogenetic investigations, and electron microscopy.
- Published
- 1994
35. Neutrophils from patients with myelodysplastic syndromes: relationship between impairment of granular contents, complement receptors, functional activities and disease status.
- Author
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Moretti S, Lanza F, Spisani S, Latorraca A, Rigolin GM, Giuliani AL, Castoldi GL, and Traniello S
- Subjects
- Chemotaxis, Leukocyte, Cytoplasmic Granules enzymology, Flow Cytometry, Humans, Lactoferrin analysis, Muramidase analysis, Myelodysplastic Syndromes enzymology, Myelodysplastic Syndromes physiopathology, Neutrophils enzymology, Neutrophils ultrastructure, Pancreatic Elastase analysis, Peroxidase analysis, Phagocytosis, Superoxides blood, Myelodysplastic Syndromes blood, Neutrophils physiology, Receptors, Complement physiology, Receptors, Complement 3b physiology
- Abstract
Myelodysplastic syndromes (MDS) are stem cell disorders of clonal origin in which infections and leukemic transformation are quite frequent. Neutrophils from 28 patients with MDS were analysed by flow cytometry for the expression of the two complement receptors CR1 and CR3, the antigenic reactivity of some granule constituents--myeloperoxidase, lysozyme, elastase, lactoferrin--and functional activities, such as locomotion, respiratory burst and cytotoxicity. The results were correlated with the FAB disease subtypes, grouped as low risk (RA) and high risk patients (RAEB, RAEB-t, CMML) and with 30 healthy subjects. A significant reduction in the percentage of neutrophil CR1, CR3 positivity and chemotaxis induced by endotoxin-activated serum was detected in the high risk group when compared with the low risk group and healthy controls. Furthermore, the high risk group also showed a low amount of myeloperoxidase, elastase, lysozyme and superoxide anion, but both low and high risk groups displayed reduced cellular cytotoxicity in comparison with the control. This work indicates that MDS patients belonging to the more advanced FAB categories frequently show multiple abnormalities in the expression of neutrophil complement receptors, and granular components (> 3), as well as in cell functions, suggesting the possibility of using these phenotypic abnormalities in the monitoring of disease progression.
- Published
- 1994
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36. Treatment of patients with acute promyelocytic leukemia. The EORTC-LCG experience. EORTC Leukemia Cooperative Group.
- Author
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Willemze R, Suciu S, Mandelli F, de Witte T, Cadiou M, Castoldi GL, Liso V, Dardenne M, Solbu G, and Zittoun R
- Subjects
- Adolescent, Adult, Female, Humans, Leukemia, Promyelocytic, Acute mortality, Male, Middle Aged, Recurrence, Remission Induction, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Promyelocytic, Acute drug therapy
- Abstract
Acute promyelocytic leukemia (M3) is, as one of the FAB subtypes of AML, included in the EORTC/GIMEMA AML-8A and 8B randomized trials. In these trials 1519 patients were included, 477 of them in non-Italian EORTC-LCG centers and 1042 in GIMEMA centers. A total of 80 patients were classified as M3 including 18 patients with M3-variant. Thirty-nine were male and 41 female. Ages ranged from 15 to 59 years; 25 (31.3%) of them were younger than 30, 34 (42.5%) between 30 and 45, and 21 (26.3%) older than 45 years of age. 56.3% of the patients had leukocytes less than 5 x 10(9)/l at the time of diagnosis vs. 24.9% of the patients belonging to the other FAB subtypes. Remission induction consisted of a standard protocol with 3 days daunorubicin and 7 days of cytosine arabinoside. Forty-three patients (53.8%) achieved a complete remission compared to 64.6% of the remaining AML patients. After salvage treatment this percentage increased to 70%, which is the same as for the other AML subtypes. Thirteen (16.3%) patients died during remission induction, mainly due to hemorrhagic complications. This percentage is significantly higher than the death rate (9.1%) in the other FAB subtypes of AML. All patients received one course of consolidation treatment. Post consolidation treatment could be either standard maintenance, intensive consolidation courses, autologous or allogeneic transplantation, according to the guidelines of the treatment protocols. At present, relapses almost all in the bone marrow, are seen in only 34.9% of the M3 patients, compared to 48.4% in the remaining AML patients. Disease-free survival for patients less than 45 years of age with the M2 and M3 subtypes was approximately 50% at 3 years compared to 30-40% for the other FAB subtypes. Despite the higher death rate during induction, the long-term survival results were better for M3 patients in comparison with the remaining AML patients. The projected survival at 3 years was 50% for M3 patients vs. 38% for remaining patients.
- Published
- 1994
37. Total loss of p53 DNA sequences in acute myeloid leukemia.
- Author
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Gandini D, Cuneo A, Carli MG, Lanza F, Castoldi GL, and del Senno L
- Subjects
- Aged, Alleles, Chromosomes, Human, Pair 17, Humans, Male, DNA, Neoplasm analysis, Gene Deletion, Genes, p53 genetics, Leukemia, Myeloid, Acute genetics
- Abstract
Mutations of the p53 tumour suppressor gene on chromosome 17p are a common genetic change in the malignant progression of many cancers. Here we report a case of a 71-year-old man with haematological, cytofluorimetric and cytochemical findings consistent with a 'de novo' M2 acute myeloid leukaemia (AML). A complex karyotype including a whole chromosome 17 and a t(17;?) (p11;?) was present in 8 of 10 metaphases of bone marrow cells. Southern blot analysis of the bone marrow DNA showed a specific loss of p53 gene in the AML cells. As far as we know, this is the first report of a deletion of both p53 alleles in leukaemia. The effect of the loss of p53 on the course of AML is discussed.
- Published
- 1994
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38. Reproducibility of the morphological diagnostic criteria for acute myeloid leukemia: the GIMEMA group experience.
- Author
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Castoldi GL, Liso V, Fenu S, Vegna ML, and Mandelli F
- Subjects
- Acute Disease, Humans, Leukemia, Myeloid classification, Reproducibility of Results, Leukemia, Myeloid pathology
- Abstract
Diagnostic reproducibility of the FAB morphological subtypes of acute leukemia is a basic step in the assessment of the clinical outcome in multicenter trials. Unusual cytologic variables and slightly different interpretations of the FAB morphological criteria have been the most significant factors affecting the overall diagnostic concordance rate among the various centers. An evaluation of the diagnostic concurrence between 35 institutions of the Italian Cooperative Study Group GIMEMA and two reviewers of the ad hoc morphological committee has been performed on 377 patients entering the AML 8A and AML 8B GIMEMA protocols. Overall concordance rate was 62.6%. The most significant differences were observed for M2 vs M4, M4 vs M5, M1 vs M2, and M2 vs M5 subtypes. In order to minimize the impact of some diagnostic deviations on the mean cytologic concordance rate, a distinction between "major" and "minor" discrepancies in the diagnostic procedures has been proposed. When the results of the single institutions were corrected by considering the "major" discrepancies only, a mean diagnostic agreement of 78.1% was reached.
- Published
- 1993
- Full Text
- View/download PDF
39. Diagnosis of leukemia: morphology.
- Author
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Castoldi GL, Cuneo A, Lanza F, and Tomasi P
- Subjects
- Humans, Leukemia classification, Leukemia, Lymphoid pathology, Leukemia, Myeloid pathology, Leukemia diagnosis, Leukemia pathology
- Published
- 1992
40. A new chromosomal breakpoint in Ph positive, bcr negative chronic myelogenous leukemia. Report of a case.
- Author
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Negrini M, Tallarico A, Pazzi I, Castagnoli A, Cuneo A, and Castoldi GL
- Subjects
- Base Sequence, Blood Cell Count, Blotting, Southern, Chromosome Mapping, Chromosomes, Human, Pair 9, Humans, Male, Middle Aged, Molecular Sequence Data, Nucleic Acid Hybridization, Polymorphism, Restriction Fragment Length, Proto-Oncogene Proteins c-bcr, Translocation, Genetic, Chromosomes, Human, Pair 22, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Protein-Tyrosine Kinases, Proto-Oncogene Proteins genetics
- Abstract
We report a new case of Ph positive chronic myeloid leukemia (CML) without the classical rearrangement in Mbcr. By Southern blot analysis the molecular breakpoint was mapped 3 to 8 kb upstream of Mbcr. This region has not been shown to be rearranged in any other described case of CML. We did not detect any specific abnormal BCR-ABL transcript even with the use of the very sensitive RNA-PCR technique.
- Published
- 1992
- Full Text
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41. Cytochemically unreactive neutrophils from subjects with myeloperoxidase (MPO) deficiency show a complex pattern of immunoreactivity with anti-MPO monoclonal antibodies: a flow cytometric and immunocytochemical study.
- Author
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Lanza F, Latorraca A, Musto P, Ferrari L, Moretti S, Zabucchi G, Carotenuto M, and Castoldi GL
- Subjects
- Antibodies, Monoclonal, Flow Cytometry, Histocytochemistry, Humans, Immunohistochemistry, Peroxidase analysis, Peroxidase immunology, Neutrophils chemistry, Peroxidase deficiency
- Abstract
Neutrophil granulocytes from 12 subjects with primary myeloperoxidase (MPO) deficiency (six totally deficient) and 16 patients with secondary partial MPO deficiency were tested using two different anti-MPO antibodies, in combination with either a flow-cytometric technique or an immunoalkaline phosphatase staining method. Results demonstrated three different cytofluorimetric patterns of immunoreactivity with the MPO protein: (a) a bright MPO antigenic expression, typical of patients with secondary MPO deficiency (comparable to that observed in the control group); (b) a medium MPO antigenic expression, typical of subjects with primary partial MPO deficiency; and (c) a dim MPO antigenic expression, characteristic of individuals with hereditary total MPO deficiency. No significant differences in granulocyte MPO reactivity were demonstrated for the two antibodies. Furthermore, in two individuals with complete primary enzyme deficiency, the single histogram analysis of MPO fluorescence determined by flow cytometry seemed to show that only 38% (case 1) and 44% (case 2) of neutrophils were reactive with the anti-MPO antibodies: the use of multiple histogram analysis in combination with Kolmogorov-Smirnov statistics allowed us to demonstrated that all the cells express a low density of MPO antigen. These data were more or less confirmed by the APAAP labeling method, which showed a reduced straining only in subjects with primary deficiency, while all patients with secondary deficiency had scores similar to those observed in controls (healthy subjects). Compared with the immunoenzymatic technique, the flow-cytometric procedure showed a higher sensitivity to MPO, being able to estimate even minor decreases in neutrophil MPO antigenic expression, as previously postulated by other authors. This work suggests that patients with primary MPO deficiency have different amounts of MPO antigens in the neutrophil granulocytes, and the levels of MPO fluorescence seem to decline concurrently with the enzyme activity, thereby suggesting the presence of a diminished MPO production. In contrast, the normal antigenic reactivity of neutrophils from patients with acquired MPO deficiency indicates the presence of a functionally inactive form of the enzyme.
- Published
- 1991
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42. Cytogenetic Findings and Survival in B-cell Chronic Lymphocytic Leukemia. Second IWCCLL Compilation of Data on 662 Patients.
- Author
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Juliusson G, Oscier D, Juliusson G, Gahrton G, Oscier D, Fitchett M, Ross F, Brito-Babapulle V, Catovsky D, Knuutila S, Elonen E, Lechleitner M, Tanzer J, Schoenwald M, Castoldi GL, Cuneo A, Nowell P, Peterson L, and Kay N
- Abstract
Chromosome analysis on CLL-cells from 649 patients revealed clonal changes in 311 cases (48%). The most common abnormalities were trisomy 12 (n = 112), and structural changes on the long arm of chromosome 13 (n = 62), most of them interstitial deletions or translocations involving 13q14, the site of the retinoblastoma gene. Complex karyotypes were associated with poor prognosis, although karyotypic changes rarely develop during the course of the disease. Among patients with single chromosomal abnormalities those with trisomy 12 had a poor survival, whereas those with structural changes on chromosome 13 had as good a prognosis as patients with a normal karyotype.
- Published
- 1991
- Full Text
- View/download PDF
43. Should alpha interferon be used as primary treatment for hairy cell leukemia? Italian Cooperative Group for Hairy Cell Leukemia.
- Author
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Capnist G, Federico M, Chisesi T, Resegotti L, Pagnucco G, Castoldi GL, Lamparelli T, Frassoldati A, Guarnaccia C, and Leoni P
- Subjects
- Humans, Leukemia, Hairy Cell mortality, Leukemia, Hairy Cell surgery, Middle Aged, Splenectomy, Interferon Type I therapeutic use, Leukemia, Hairy Cell drug therapy
- Abstract
To answer the question of whether interferon (IFN) should replace splenectomy, we reviewed the Italian HCL Registry: the records of 450 patients with hairy cell leukemia (HCL), seen from 1975 to 1988 were analysed. Of these, 321 were considered for the study: 231 had been splenectomized, 46 of them receiving subsequently IFN and 90 patients had IFN as initial therapy. Patients treated with splenectomy showed different survival according to Jansen and Hermans' staging system, which identified two risk groups: stage 1 and stages 2 and 3, p = 0.0329. On the contrary, patients treated with IFN did not show significantly different survival according to stage. By the comparison of stage 1 patients, either treated with splenectomy or with IFN, no statistical difference in survival was registered. Different survivals emerged for patients stage 2 + 3, which improved when treated with IFN, p = 0.0324. The median failure free survival (FFS) after splenectomy resulted in 89 months versus 33 months after IFN. In conclusion, splenectomy still remains the primary therapy for HCL patients stage 1. For high risk patients, stages 2 and 3, IFN should be adopted as first line therapy, improving substantially the survival. The short duration of response to IFN suggests a sequential combination of the two treatments for this group of patients, IFN reducing tumor mass quite safely and splenectomy assuring long lasting stable disease.
- Published
- 1991
- Full Text
- View/download PDF
44. Evaluation of CR1 expression in neutrophils from chronic myeloid leukaemia: relationship between prognosis and cellular activity.
- Author
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Lanza F, Fagioli F, Gavioli R, Spisani S, Malavasi F, Castoldi GL, and Traniello S
- Subjects
- Cytotoxicity, Immunologic, Humans, Immunoenzyme Techniques, Interferon alpha-2, Interferon-alpha therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive immunology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Neutrophils metabolism, Neutrophils physiology, Prognosis, Receptors, Complement 3b, Recombinant Proteins, Complement C3b metabolism, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism, Neutrophils immunology, Receptors, Complement analysis
- Abstract
The expression of the complement receptor CR1 has been evaluated using an immunoalkaline phosphatase staining method on peripheral blood neutrophils and granulocyte precursors from 22 patients with chronic myeloid leukaemia (CML) and 15 healthy subjects. The immunocytochemical labelling pattern of CR1 was evaluated semiquantitatively on cell smears using three different anti-CR1 monoclonal antibodies. The scoring method showed that seven patients with CML had a marked reduction in CR1 expression which did not change with in vitro stimulation of neutrophils with phorbol-myristate-acetate (PMA) whereas control cells responded to PMA, increasing the receptor level two-fold. In addition, functional analysis of neutrophils with low CR1 expression from CML patients showed a very low cytolytic activity against K562 tumour target, suggesting a relationship between the cellular content of CR1 and neutrophil tumouricidal activity. The involvement of CR1 in neutrophil-mediated lysis is consistent with complete lack of tumour toxicity following receptor neutralization by anti-CR1 monoclonal antibodies. Interferon therapy improved CR1 expression and the cytolytic response of neutrophils in three out of five CML patients with a moderately low CR1 score. CML patients non-responding to interferon therapy and those with a very low CR1 score, independent of the clinical stage, progressed more rapidly into the advanced clinical stage and blastic crisis.
- Published
- 1991
- Full Text
- View/download PDF
45. Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosomal abnormalities.
- Author
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Juliusson G, Oscier DG, Fitchett M, Ross FM, Stockdill G, Mackie MJ, Parker AC, Castoldi GL, Guneo A, Knuutila S, Elonen E, and Gahrton G
- Subjects
- Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 14, Female, Humans, Karyotyping, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Male, Metaphase, Middle Aged, Multicenter Studies as Topic, Prognosis, Survival Rate, Trisomy, Chromosome Aberrations, Leukemia, Lymphocytic, Chronic, B-Cell mortality
- Abstract
Background and Methods: Specific chromosomal abnormalities have been shown to affect the overall survival of patients with acute leukemia, but the possibility that specific chromosomal defects may influence the course of B-cell chronic lymphocytic leukemia (CLL) is controversial. We assessed this possibility as follows: blood mononuclear cells from 433 patients with B-cell CLL in five European centers were cultured with B-cell mitogens, and banded metaphases were studied., Results: Three hundred ninety-one patients could be evaluated cytogenetically, and 218 had clonal chromosomal changes. The most common abnormalities were trisomy 12 (n = 67) and structural abnormalities of chromosome 13 (n = 51; most involving the site of the retinoblastoma gene) and of chromosome 14 (n = 41). Patients with a normal karyotype had a median overall survival of more than 15 years, in contrast to 7.7 years for patients with clonal changes. Patients with single abnormalities (n = 113) did better than those with complex karyotypes (P less than 0.001). Patients with abnormalities involving chromosome 14q had poorer survival than those with aberrations of chromosome 13q (P less than 0.05). Among patients with single abnormalities, those with trisomy 12 alone had poorer survival than patients with single aberrations of chromosome 13q (P = 0.01); the latter had the same survival as those with a normal karyotype. A high percentage of cells in metaphase with chromosomal abnormalities, indicating highly proliferative leukemic cells, was associated with poor survival (P less than 0.001). Cox proportional-hazards analysis identified age, sex, the percentage of cells in metaphase with chromosomal abnormalities, and the clinical stage of the disease (Binet classification system) as independent prognostic variables., Conclusions: Chromosomal analysis provides prognostic information about overall survival in addition to that supplied by clinical data in patients with B-cell CLL.
- Published
- 1990
- Full Text
- View/download PDF
46. Chronic myelogenous leukemia with typical clinical and morphological features can be Philadelphia chromosome negative and "bcr negative".
- Author
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Selleri L, Emilia G, Luppi M, Temperani P, Zucchini P, Tagliafico E, Artusi T, Sarti M, Donelli A, and Castoldi GL
- Subjects
- Adult, Aged, Blotting, Northern, Blotting, Southern, DNA, Neoplasm blood, DNA, Neoplasm genetics, DNA, Neoplasm isolation & purification, Female, Humans, Male, Middle Aged, RNA, Neoplasm genetics, RNA, Neoplasm isolation & purification, Restriction Mapping, Fusion Proteins, bcr-abl genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative genetics
- Abstract
The Philadelphia (Ph1) chromosome is found in the majority of patients affected by chronic myelogenous leukemia (CML), being considered the hallmark of the disease, but around 5-8% of patients diagnosed as CML lack the Ph1 chromosome-negative (Ph-) CML has been discussed extensively in the literature because of its heterogeneity. However, it is now accepted that some of the Ph1-CML patients have a disease indistinguishable from Ph1-positive (Ph+) CML. It was investigated whether Ph- CML with clinical and morphological features indicating true CML would always have bcr rearrangements, as the relocation of c-abl from 9q34 into the breakpoint cluster region on 22q11 is considered a crucial event in the pathogenesis of CML. From molecular studies, it seemed that Ph- CML with features of true CML always have the bcr rearrangement, while Ph- patients, lacking such rearrangement, have atypical forms of CML. Here we describe 8 Ph- CML and myeloproliferative syndrome (MPS) patients of whom 6 were by all respects true CML cases. Nevertheless, bcr rearrangement and expression of the classic bcr/abl chimeric mRNA was found in only 1 of the 6 patients. More advanced molecular techniques will be needed to understand which molecular mechanisms underlie Ph-, bcr- CML, resulting in phenotypes sometimes indistinguishable from Ph+, bcr+ CML.
- Published
- 1990
47. Automated assessment of lymphoid cells in chronic lymphocytic leukemia: correlation with prognostic features.
- Author
-
Lanza F, Scapoli GL, Spanedda R, Franzé D, and Castoldi GL
- Subjects
- Aged, Female, Flow Cytometry, Humans, Leukemia, Lymphoid blood, Male, Middle Aged, Prognosis, Leukemia, Lymphoid diagnosis, Lymphocytes classification
- Published
- 1985
48. Cytogenetically distinct leukemic cell lines displaying in vitro specific proliferative and differentiation capacities may account for early disease relapse in the blast phase of CML.
- Author
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Barbieri D, Ferraresi P, Spanedda R, and Castoldi GL
- Subjects
- Adult, Cell Differentiation, Cell Division, Cell Line, Humans, Karyotyping, Leukemia, Myeloid genetics, Male, Prognosis, Recurrence, Time Factors, Leukemia, Myeloid pathology
- Abstract
The cytogenetic features and the proliferative and differentiation capabilities of blast cell fractions purified on a density gradient were studied in one patient with chronic myeloid leukemia (CML) in blast crisis, both at the emergence and at relapse of the disease. The results show that relapse was due to the appearance of a new leukemic cell line that was characterized by peculiar chromosomal, growth, and differentiation features, which seemingly accounted for early refractoriness to therapy and disease progression.
- Published
- 1985
- Full Text
- View/download PDF
49. Human lymphoblastoid interferon for hairy cell leukemia: results from the Italian Cooperative Group.
- Author
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Damasio EE, Bernasconi C, Castoldi GL, Chisesi T, Federico M, Lamparelli T, Lauria F, Pagnucco G, Resegoti L, and Rossi E
- Subjects
- Humans, Leukemia, Hairy Cell pathology, Leukocyte Count, Platelet Count, Spleen pathology, Interferon Type I therapeutic use, Leukemia, Hairy Cell therapy
- Abstract
Since April 1985, 82 patients with HCL entered a multicenter study using lymphoblastoid alpha-interferon; 51 (including 15 who failed splenectomy and 24 with substantial splenomegaly) enrolled before April 1986 are evaluated in this study. The patients were treated with 3 mega units daily subcutaneously until complete or partial response and were thereafter randomly allocated to a maintenance regime of 3 mega units/week or to observation only. Ten cases had a complete response, 18 a partial response, and 15 a minimal response. Two patients had no response, two interrupted therapy due to major toxicity (toxic hepatitis and thrombocytopenia), six died before completing 1 month of therapy of sepsis, and two died of myocardial infarction. In the two groups of splenectomized and nonsplenectomized patients the mean time to hemoglobin recovery was 8.5 and 6.5 weeks, respectively, the neutrophil count recovery was 6.5 and 9.3 weeks, and the time to platelet count recovery was 4.0 and 5.4 weeks, respectively. No significant differences in recovery time and response rate were observed between the two groups. In 31 out of 32 patients with substantial splenomegaly the spleen became either inpalpable (18) or significantly smaller (13). This study confirms the responsiveness of HCL to IFN in nonsplenectomized patients with high tumor burdens and is therefore recommended as a first-line therapy.
- Published
- 1987
50. Nuclear projections in tumour cells and large chromosome markers.
- Author
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Castoldi GL, Grusovin GD, Gualandi M, and Scapoli GL
- Subjects
- Chromosomes, Human, 1-3, Histiocytes, Humans, Mitosis, Pleural Effusion cytology, Chromosome Aberrations, Chromosome Disorders, Sarcoma pathology
- Abstract
The application of banding techniques on cytological smears from pleural effusion in a case of histiocytic sarcoma has provided direct evidence for correspondence between nuclear projections in tumour cells and extra large chromosome markers observed in the neoplastic karyotype obtained by direct preparations.
- Published
- 1976
- Full Text
- View/download PDF
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