11 results on '"Detlef Haase"'
Search Results
2. Frequency and prognostic impact of casein kinase 1A1 mutations in MDS patients with deletion of chromosome 5q
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Katayoon Shirneshan, Sabine Cerny-Reiterer, Christina Ganster, Detlef Haase, Gudrun Göhring, T Haferlach, Christian Thiede, N. Kroeger, Jana Fabisch, Claudia Haferlach, U. Platzbecker, L Köhler, V Panagiota, Peter Valent, Annika Gutermuth, Sabrina Klesse, Arnold Ganser, Steve Ehrlich, Brigitte Schlegelberger, Michael Heuser, Jan Krönke, Felicitas Thol, Kathrin Stamer, Christian Koenecke, Manja Meggendorfer, Guido Kobbe, Michelle Maria Araujo Cruz, Tobias Schroeder, and Konstanze Döhner
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Genetics ,Cancer Research ,Mutation ,Chromosome ,Casein Kinase Ialpha ,Hematology ,Biology ,medicine.disease_cause ,Prognosis ,Molecular biology ,3. Good health ,Oncology ,hemic and lymphatic diseases ,Myelodysplastic Syndromes ,medicine ,Chromosomes, Human, Pair 5 ,Humans ,Casein kinase 1 ,Chromosome Deletion - Abstract
Frequency and prognostic impact of casein kinase 1A1 mutations in MDS patients with deletion of chromosome 5q
- Published
- 2015
3. Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS)
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Christa Fonatsch, Michael Lübbert, Andrea Kündgen, Corinna Strupp, Norbert Gattermann, Detlef Haase, Thomas Nösslinger, Otto Krieger, Reinhard Stauder, Christian Steidl, Carlo Aul, Michael Pfeilstöcker, Peter Valent, Ulrich Germing, Rainer Haas, Aristoteles Giagounidis, T Mueller, and Barbara Hildebrandt
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Prognostic variable ,Adolescent ,urologic and male genital diseases ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Risk factor ,Survival rate ,Aged ,Retrospective Studies ,Aged, 80 and over ,L-Lactate Dehydrogenase ,business.industry ,Myelodysplastic syndromes ,Retrospective cohort study ,Hematology ,Clinical Enzyme Tests ,Middle Aged ,Models, Theoretical ,Prognosis ,medicine.disease ,3. Good health ,Surgery ,Survival Rate ,International Prognostic Scoring System ,Myelodysplastic Syndromes ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Female ,business ,Risk assessment ,030215 immunology ,French–American–British classification - Abstract
The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian-German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P
- Published
- 2005
4. Cytogenetic subgroups in acute myeloid leukemia differ in proliferative activity and response to GM-CSF
- Author
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C. Fonatsch, Wolfgang Hiddemann, Bernhard Wörmann, Jan Braess, Detlef Haase, G Jahns-Streubel, Claudia Binder, T. Büchner, and Claudia Schoch
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Cancer Research ,medicine.medical_specialty ,Alpha (ethology) ,Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,030304 developmental biology ,0303 health sciences ,Cytogenetics ,Granulocyte-Macrophage Colony-Stimulating Factor ,Myeloid leukemia ,Hematology ,Deoxycytidine kinase ,medicine.disease ,Molecular biology ,Deoxycytidine deaminase ,3. Good health ,Leukemia ,Treatment Outcome ,medicine.anatomical_structure ,Granulocyte macrophage colony-stimulating factor ,Oncology ,Leukemia, Myeloid ,Karyotyping ,030220 oncology & carcinogenesis ,Acute Disease ,Immunology ,Bone marrow ,Cell Division ,medicine.drug - Abstract
The current study was undertaken to search for differences in the biology of cytogenetic subgroups in patients with de novo acute myeloid leukemia (AML). In addition, factors influencing the metabolism of cytosine arabinoside (araC) as the key agent of antileukemic activity were assessed. Bone marrow aspirates from 91 patients with newly diagnosed AML in whom karyotypes were successfully obtained were analyzed: (1) for spontaneous proliferative activity by 3H-thymidine (3H-TdR) incorporation; (2) proliferative response to GM-CSF by in vitro incubation of blasts for 48 h with or without GM-CSF (100 U/ml) followed by an additional 4-h exposure to 3H-TdR (0.5 microCi/ml); and (3) parameters of araC metabolism comprising 3H-araC uptake in vitro and the activities of polymerase alpha (poly alpha), deoxycytidine kinase (DCK) and deoxycytidine deaminase (DCD). According to the results of chromosome analyses four cytogenetic subgroups were discriminated: (I) normal karyotypes (n = 38); (II) favorable karyotypes [t8;21), t(15;17), inv(16)] (n = 16); (III) unfavorable karyotypes [inv (3), -5, 5q-, t(6;9), +8, t (9;11), complex abnormalities] (n = 20); (IV) karyotypes of unknown prognostic significance (n = 17). Proliferative activity of leukemic blasts was significantly higher in favorable karyotypes (group II) as compared to cases with unfavorable cytogenetics (group III) with median values and range for 3H-TdR uptake in group II of 2.48 pmol/10(5) cells (0.28-25.8) and in group III of 0.51 pmol/10(5) cells (0.04-7.6) (P = 0.0096). The respective values in group I and group IV were 0.7pmol/10(5) cells (0.0-6.7) and 0.98 pmol/10(5) cells (0.0-4.0), respectively. Inversely, response to GM-CSF, as defined by an increase in 3H-TdR incorporation >1.5- fold over control values after 48h of GM-CSF exposure, was significantly lower for patients with a favorable karyotype (group II) as compared to group I (P = 0.04) and group III (P = 0.013). No significant differences between karyotype groups I, II, III and IV were found for 3H-araC incorporation, nor for the activities of poly alpha, DCK and DCD. These data demonstrate differences in the biology of cytogenetic subgroups in AML which may partly explain the well established differences in clinical outcome.
- Published
- 2001
5. Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia
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Peter Staib, C. Fonatsch, Axel Heyll, Winfried Gassmann, C. Schoch, T Haferlach, Andreas Hochhaus, Carlo Aul, Ruediger Hehlmann, Dietrich W. Beelen, Wolfgang Hiddemann, Bernhard Wörmann, W.-D. Ludwig, Achim Heinecke, Detlef Haase, Helmut Löffler, Wolfgang Seifarth, Maria-Cristina Sauerland, A. Reichert, Eva Lengfelder, Th. Büchner, and Susanne Saussele
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Oncology ,Acute promyelocytic leukemia ,Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Antimetabolite ,03 medical and health sciences ,0302 clinical medicine ,Maintenance therapy ,Tretinoin ,Internal medicine ,medicine ,Chemotherapy ,business.industry ,Induction chemotherapy ,Hematology ,medicine.disease ,Minimal residual disease ,3. Good health ,Surgery ,030220 oncology & carcinogenesis ,Cytarabine ,business ,030215 immunology ,medicine.drug - Abstract
A prospective multicenter study was performed to investigate the clinical and molecular results of intensified double induction therapy including high-dose cytarabine (ara-C) in combination with ATRA in newly diagnosed acute promyelocytic leukemia (APL), followed by consolidation and 3 years maintenance therapy. Fifty-one patients, diagnosed and monitored from December 1994 to June 1999, were evaluated. The median age was 43 (16–60) years. The morphologic diagnosis was M3 in 40 (78%) and M3v in 11 (22%) patients. In 15 (30%) patients the initial white blood cell counts were ⩾5 × 109/l. The cytogenetic or molecular proof of the translocation t(15;17) was a mandatory prerequisite for eligibility. The diagnosis was confirmed by karyotyping in 46 and by RT-PCR of the PML/RARα transcript in 45 cases. The rate of complete hematological remission was 92% and the early death rate 8%. Monitoring of minimal residual disease by RT-PCR of PML/RARα (sensitivity 10−4) showed negativity in 29 of 32 (91%) evaluable cases after induction, in 23 of 25 (92%) after consolidation, and in 27 of 30 (90%) during maintenance, after a median time of 2, 4 and of 18 months after diagnosis, respectively. After a median follow-up of 27 months, the estimated actuarial 2 years overall and event-free survival were both 88% (79, 97), and the 2 years relapse-free survival 96% (90, 100). The high antileukemic efficacy of this treatment strategy is demonstrated by a rapid and extensive reduction of the malignant clone and by a low relapse rate. The results suggest that the intensity of the induction chemotherapy combined with ATRA is one of the factors which may have a critical influence on the outcome of APL. A randomized trial should assess the value of an induction therapy including ATRA and high-dose ara-C in comparison to standard-dose ara-C.
- Published
- 2000
6. Intensive consolidation versus oral maintenance therapy in patients 61 years or older with acute myeloid leukemia in first remission: results of second randomization of the AML HD98-B treatment Trial
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H Salwender, R Schoch, Christoph Nerl, Hartmut Döhner, Axel Glasmacher, Katharina Götze, Hans G. Mergenthaler, Manfred Hensel, F. Hartmann, Richard F. Schlenk, Stefan Fröhling, Elisabeth Koller, H G Biedermann, J. Th. Fischer, Heinz Kirchen, Detlef Haase, Axel Benner, Konstanze Döhner, Stephan Kremers, F. Del Valle, Axel Matzdorff, and Hans Pralle
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Cancer Research ,medicine.medical_specialty ,Randomization ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Maintenance therapy ,law ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Idarubicin ,Mitoxantrone ,business.industry ,Myeloid leukemia ,Hematology ,medicine.disease ,3. Good health ,Surgery ,Clinical trial ,Leukemia ,Oncology ,030220 oncology & carcinogenesis ,business ,030215 immunology ,medicine.drug - Abstract
Intensive consolidation versus oral maintenance therapy in patients 61 years or older with acute myeloid leukemia in first remission: results of second randomization of the AML HD98-B treatment Trial
- Published
- 2006
7. Cytogenetic analysis of CD34+ subpopulations in AML and MDS characterized by the expression of CD38 and CD117
- Author
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C. Schäfer, Claudia Schoch, Detlef Haase, Wolfgang Hiddemann, B. Gahn, C. Troff, Michaela Feuring-Buske, and Bernhard Wörmann
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Adult ,Male ,Cancer Research ,Centromere ,CD34 ,Antigens, CD34 ,Stem cell factor ,Biology ,Models, Biological ,Immunophenotyping ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,Antigens, CD ,Bone Marrow ,Cancer stem cell ,hemic and lymphatic diseases ,Humans ,Progenitor cell ,ADP-ribosyl Cyclase ,N-Glycosyl Hydrolases ,Aged ,Membrane Glycoproteins ,CD117 ,Hematology ,Middle Aged ,Flow Cytometry ,Hematopoietic Stem Cells ,ADP-ribosyl Cyclase 1 ,Antigens, Differentiation ,3. Good health ,Leukemia, Myeloid, Acute ,Proto-Oncogene Proteins c-kit ,Cell Transformation, Neoplastic ,Oncology ,Karyotyping ,Myelodysplastic Syndromes ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Female ,Stem cell ,Chromosomes, Human, Pair 8 ,030215 immunology - Abstract
It has been supposed in de novo AML that malignant transformation occurs at the level of committed progenitors. Recent data of our group and others provide evidence that in AML malignant transformation may regularly occur at the level of stem cells. These cells can be discriminated by function and specific surface molecules. CD34, a glycophosphoprotein, is a cellular surface antigen characteristically expressed by stem cells. CD34+ stem cells can be further subdivided by the expression of additional surface molecules like CD38 and CD117. In this article we present results from cytogenetic examinations of FACS-isolated stem cell subpopulations in eight patients (four AML and four MDS). Six of them displayed clonal karyotype abnormalities at the time of first diagnoses in the native bone marrow (5q-; 5q- and complex abnormalities; +8; inv(16) and +8; i(17q) and -21; i(21q)). We used CD117, the receptor for the stem cell factor (also KIT oncogene) as a new cellular surface marker. CD34+/CD117+/- stem cell subpopulations were examined in two patients with AML and three patients with MDS. We found leukemic stem cells in every type of stem cell subpopulation examined (CD34+/CD38-, CD34+/CD38+, CD34+/CD117-, CD34+/CD117+). Secondary, progression-associated chromosome abnormalities likewise were demonstrable in CD34+ cells. In three patients a mosaic of normal and abnormal metaphases was found in the highly purified stem cell subpopulations. We conclude that in AML and MDS stem cells are the target of leukemogenic genetic defects. CD117 as a new marker to isolate different CD34+ subpopulations was not sufficient to discriminate between normal and leukemic stem cells. Our findings have implications for autologous stem cell transplantation, high-dose chemotherapy and the pathogenetic concept of leukemogenesis.
- Published
- 1997
8. Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): a multicenter study
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Michael Pfeilstöcker, Ulrich Germing, Rainer Haas, John F. Seymour, Carlo Aul, Charikleia Kelaidi, Mikkael A. Sekeres, Julie Schanz, Detlef Haase, Sabine Blum, Karl-Anton Kreuzer, Aristoteles Giagounidis, Otto Krieger, Peter Valent, R Weide, Jaroslaw P. Maciejewski, Michael Lauseker, Arnold Ganser, Katharina Götze, Pierre Fenaux, Richard F. Schlenk, Wolf-K. Hofmann, Andrea Kündgen, Melita Kenealy, Barbara Hildebrandt, Jaroslav Cermak, Uwe Platzbecker, Joerg Hasford, Reinhard Stauder, Thomas Nösslinger, Argiris Symeonidis, and Michael Lübbert
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Pediatrics ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Preleukemia ,Registries ,Survival rate ,Aged ,Retrospective Studies ,Aged, 80 and over ,Framingham Risk Score ,business.industry ,Myelodysplastic syndromes ,Myeloid leukemia ,Retrospective cohort study ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,3. Good health ,Survival Rate ,Cell Transformation, Neoplastic ,Multicenter study ,International Prognostic Scoring System ,030220 oncology & carcinogenesis ,Myelodysplastic Syndromes ,Disease Progression ,Chromosomes, Human, Pair 5 ,Female ,Chromosome Deletion ,business ,030215 immunology - Abstract
Myelodysplastic syndromes (MDS) with del(5q) are considered to have a benign course of the disease. In order to address the issue of the propensity of those patients to progress to acute myeloid leukemia (AML), data on 381 untreated patients with MDS and del(5q) characterized by low or intermediate I International Prognostic Scoring System (IPSS) risk score were collected from nine centers and registries. Median survival of the entire group was 74 months. Transfusion-dependent patients had a median survival of 44 months vs 97 months for transfusion-independent patients (P0.0001). Transfusion need at diagnosis was the most important patient characteristic for survival. Of the 381 patients, 48 (12.6%) progressed to AML. The cumulative progression rate calculated using the Kaplan-Meier method was 4.9% at 2 years and 17.6% at 5 years. Factors associated with the risk of AML transformation were high-risk World Health Organization adapted Prognostic Scoring System (WPSS) score, marrow blast count5% and red-cell transfusion dependency at diagnosis. In conclusion, patients with MDS and del(5q) are facing a considerable risk of AML transformation. More detailed cytogenetic and molecular studies may help to identify the patients at risk of progression.
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- 2012
9. Combined analysis of ZAP-70 and CD38 expression as a predictor of disease progression in B-cell chronic lymphocytic leukemia
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Frank Griesinger, Lorenz Trümper, Jan Dürig, Ludger Klein-Hitpass, Ulrich Dührsen, B Kulle, Detlef Haase, Ludger Sellmann, and Roland Schroers
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Oncology ,Male ,Cancer Research ,Chronic lymphocytic leukemia ,Medizin ,CD38 ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,In Situ Hybridization, Fluorescence ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Aged, 80 and over ,0303 health sciences ,Hematology ,Membrane Glycoproteins ,ZAP-70 Protein-Tyrosine Kinase ,biology ,Gene Expression Regulation, Leukemic ,hemic and immune systems ,Middle Aged ,Protein-Tyrosine Kinases ,Leukemia ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Antibody ,Immunoglobulin Heavy Chains ,Adult ,medicine.medical_specialty ,chemical and pharmacologic phenomena ,Gene Expression Regulation, Enzymologic ,03 medical and health sciences ,Antigens, CD ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,ADP-ribosyl Cyclase ,Survival analysis ,030304 developmental biology ,Aged ,Chromosome Aberrations ,Gene Expression Profiling ,Reproducibility of Results ,medicine.disease ,ADP-ribosyl Cyclase 1 ,Leukemia, Lymphocytic, Chronic, B-Cell ,Survival Analysis ,Gene expression profiling ,Immunology ,Mutation ,biology.protein - Abstract
Prognostic predictions in B-cell chronic lymphocytic leukemia (B-CLL) at early clinical stage are based on biological disease parameters, such as ZAP-70 and CD38 protein levels, genomic aberrations as well as immunoglobulin variable heavy chain gene (IgV(H)) mutation status. In the current study, ZAP-70 and CD38 expressions were examined by flow cytometry in 252 patients with B-CLL. Cytoplasmic ZAP-70 expression in more than 20% (ZAP-70(+)) and surface CD38 expression on more than 30% (CD38(+)) of B-CLL cells were associated with an unfavorable clinical course. The levels of ZAP-70 and CD38 did not change over time in the majority of patients where sequential samples were available for analysis. Combined analysis of ZAP-70 and CD38 yielded discordant results in 73 patients (29.0%), whereas 120 patients (47.6%) were concordantly negative and 59 patients (23.4%) were concordantly positive for ZAP-70 and CD38 expression. Median treatment-free survival times in patients whose leukemic cells were ZAP-70(+)CD38(+) was 30 months as compared to 130 months in patients with a ZAP-70(-)CD38(-) status. In patients with discordant ZAP-70/CD38 results, the median treatment-free survival time was 43 months. Thus, ZAP-70 and CD38 expression analyses provided complementary prognostic information identifying three patient subgroups with good, intermediate and poor prognosis. Over-representation of high-risk genomic aberrations such as 17p deletion or 11q deletion and distribution of the IgV(H) mutation status in B-CLL discordant for ZAP-70/CD38 pointed toward a distinct biologic background of the observed disease subgroups. This finding was also supported by microarray-based gene expression profiling in a subset of 35 patients. The expression of 37 genes differed significantly between the three groups defined by their expression of ZAP-70 and CD38, including genes that are involved in regulation of cell survival and chemotherapy resistance.
- Published
- 2005
10. Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML
- Author
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Susanne Schnittger, Achim Heinecke, Frank Griesinger, T Haferlach, Claudia Schoch, U Kinkelin, Th. Büchner, Detlef Haase, Wolfgang Hiddemann, and Bernhard Wörmann
- Subjects
Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Aneuploidy ,MLL Partial Tandem Duplication ,Trisomy ,Biology ,Bioinformatics ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,Gene Duplication ,Gene duplication ,Antineoplastic Combined Chemotherapy Protocols ,Proto-Oncogenes ,medicine ,Humans ,Child ,neoplasms ,BAALC ,030304 developmental biology ,Aged ,0303 health sciences ,Chromosomes, Human, Pair 11 ,Cytogenetics ,Myeloid leukemia ,Chromosome Mapping ,Hematology ,Exons ,Histone-Lysine N-Methyltransferase ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,3. Good health ,DNA-Binding Proteins ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,Karyotyping ,Female ,Tandem exon duplication ,Myeloid-Lymphoid Leukemia Protein ,Transcription Factors - Abstract
Partial tandem duplications of the MLL gene have been associated with trisomy 11 in acute myeloid leukemia (AML) and recently, have also been reported for karyotypically normal AML. In order to test the incidence and prognostic importance of this molecular marker, we have analyzed eight cases of AML with trisomy 11 and 387 unselected consecutive cases with AML for partial duplications of the MLL gene. Patients with normal karyotypes and those with various chromosome aberrations were included. De novo as well as secondary leukemias including all FAB subtypes were analyzed. Performing a one-step RT-PCR with 35 cycles using an exon 9 forward primer and an exon 3 reverse primer partial tandem duplications of the MLL gene were demonstrated in 3/8 (37.5%) patients with trisomy 11. In addition, 13/387 (3.4%) of unselected cases revealed a tandem duplication. Ten of these 13 cases were cytogenetically normal, the other three cases had < or =2 additional chromosomal alterations. Sequencing of the RT-PCR products of all 16 positive cases revealed fusions of MLL exon 9/exon 3 (e9/e3) (six cases), e10/e3 (three cases), e11/e3 (four cases) or combinations of differentially spliced e10/e3 and e11/e3 (three cases) transcripts. The duplications were confirmed by genomic long range PCR and Southern blot hybridization. Twelve cases with the MLL duplication were de novo myeloid leukemia, one was a secondary AML after MDS, three were therapy-related AML (t-AML). Of the 16 MLL-duplication positive cases, seven were classified as FAB M2, two as M1, five as M4, one as M0, one as M5b. The mean age was 62.3 years for patients with MLL duplication vs 50.3 years for the control group. Of 15 adult patients, 12 received treatment. Of these, three were nonresponders, five had early relapse (< or =6 months), four relapsed between 7 and 12 months. Median survival and relapse-free interval of the MLL duplication positive group was significantly worse than those of an age-matched karyotypically normal control group. In conclusion, MLL tandem duplications (1) are less common than previously reported; (2) are preferentially observed in AML with normal karyotypes, but can also be found in the presence of chromosome alterations; (3) are not strongly associated with an FAB subtype; (4) were not observed with the prognostically favorable t(8;21), inv(16), and t(15;17), other recurrent translocations, or in complex karyotypes; and (5) identifies a subgroup of patients with an unfavorable prognosis.
- Published
- 2000
11. Clonal chromosomal abnormalities in the stem cell compartment of patients with acute myeloid leukemia in morphological complete remission
- Author
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Wolfgang Hiddemann, Michaela Feuring-Buske, Detlef Haase, Bernhard Wörmann, and Christian Buske
- Subjects
Adult ,Cancer Research ,Pathology ,medicine.medical_specialty ,Neoplasm, Residual ,CD34 ,Antigens, CD34 ,Chromosome Disorders ,Cell Separation ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Immunophenotyping ,NAD+ Nucleosidase ,Antigens, CD ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,ADP-ribosyl Cyclase ,Cells, Cultured ,030304 developmental biology ,Chromosome Aberrations ,0303 health sciences ,Acute leukemia ,Membrane Glycoproteins ,Remission Induction ,Myeloid leukemia ,Hematology ,medicine.disease ,Flow Cytometry ,Hematopoietic Stem Cells ,Minimal residual disease ,ADP-ribosyl Cyclase 1 ,Antigens, Differentiation ,3. Good health ,Leukemia ,medicine.anatomical_structure ,Oncology ,Leukemia, Myeloid ,030220 oncology & carcinogenesis ,Karyotyping ,Acute Disease ,Bone marrow ,Stem cell - Abstract
Acute myeloid leukemia arises from the clonal expansion of a malignant transformed progenitor cell. Despite intensive chemotherapy, final disease eradication is achieved by a small proportion of cases only and 50-70% of adults with AML will ultimately relapse and die from their disease. Hence residual disease below the level of morphological detectability must be assumed in clinical and morphological complete remission. CD34+/CD38- and CD34+/CD38+ subpopulations of seven patients in morphological complete remission were isolated by FACS (purity98%) and were analyzed by conventional cytogenetics or FISH for chromosomal aberrations. In five of seven patients, clonal chromosomal abnormalities were detected in the CD34+/CD38+ subpopulation and in one patient with AML M2 (add (2)(q37)) in the most immature CD34+/CD38- stem cell compartment. One patient with AML M4Eo (inv(16),+8), showed a normal karyotype by conventional cytogenetic analysis, whereas four of 15 metaphases of the sorted CD34+/CD38+ subpopulation revealed the inversion 16. These observations underline that leukemic cells can survive intensive chemotherapy in the niche of the stem cell compartment. In some patients the sensitivity for the detection of persistent leukemic cells seems to be higher in FACS-sorted subpopulations than conventional cytogenetic analysis of the unseparated bone marrow. Immunophenotyping revealed minimal residual disease in four of the patients. Functional analysis has to be performed to investigate the leukemogenic potential of these residual cells.
- Published
- 1999
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