32 results on '"Murata-Collins, J."'
Search Results
2. Therapy-Related Myelodysplasia: Somatic Mutations and Allogeneic Hematopoietic Cell Transplantation Outcomes
- Author
-
Nakamura, R., primary, Pham, A., additional, Gendzekhadze, K., additional, Min, L., additional, Pullarkat, V., additional, Al Malki, M., additional, O Donnell, M., additional, Cao, T., additional, Stein, A., additional, Khaled, S., additional, Ali, H., additional, Senitzer, D., additional, Michelle Afkhami, M.A., additional, Aoun, P., additional, Murata-Collins, J., additional, Forman, S., additional, Palmer, J., additional, Marcucci, G., additional, Pillai, R., additional, and Aldoss, I., additional
- Published
- 2017
- Full Text
- View/download PDF
3. 63 - Therapy-Related Myelodysplasia: Somatic Mutations and Allogeneic Hematopoietic Cell Transplantation Outcomes
- Author
-
Nakamura, R., Pham, A., Gendzekhadze, K., Min, L., Pullarkat, V., Al Malki, M., O Donnell, M., Cao, T., Stein, A., Khaled, S., Ali, H., Senitzer, D., Michelle Afkhami, M.A., Aoun, P., Murata-Collins, J., Forman, S., Palmer, J., Marcucci, G., Pillai, R., and Aldoss, I.
- Published
- 2017
- Full Text
- View/download PDF
4. Phase 1 Dose Escalation Trial of Total Marrow and Lymphoid Irradiation (TMLI) Using Helical Tomotherapy Combined With Etoposide (VP16) and Cyclophosphamide (CY) in Patients With Refractory Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation (alloHCT)
- Author
-
Wong, J.Y., primary, Stein, A., additional, Palmer, J.M., additional, Liu, A., additional, O'Donnell, M., additional, Schultheiss, T., additional, Radany, E., additional, Snyder, D.S., additional, Tsai, N., additional, Parker, P., additional, Farol, L., additional, Spielberger, R., additional, Sahebi, F., additional, Murata-Collins, J., additional, Senitzer, D., additional, and Forman, S., additional
- Published
- 2014
- Full Text
- View/download PDF
5. Interphase Spectral FISH: Tailoring a diagnostic and minimal residual disease (MRD) assay for oncology
- Author
-
Murata-Collins, J L, primary, Zhang, F, additional, Tcheurekdiian, L, additional, and Slovak, M L, additional
- Published
- 2000
- Full Text
- View/download PDF
6. Minimal residual disease (MRD) in remission t(8;21) AML and in vivo differentiation detected by FISH and CD34+ cell sorting.
- Author
-
Varella-Garcia, M, Hogan, C J, Odom, L F, Murata-Collins, J L, Ai, H, Chen, L, Richkind, K, Paskulin, G, Andreeff, M, Brizard, A, McGavran, L, Gemmill, R M, Berger, R, and Drabkin, H A
- Subjects
ACUTE myeloid leukemia ,CHROMOSOMES - Abstract
Many patients with t(8;21) AML have residual positive cells during remission. We previously developed D-FISH probes that detect both derivative chromosomes and the normal alleles. In negative controls, only 2/44,000 (0.0045%) positive signals were observed. To investigate MRD, we examined specimens from 29 patients who had initially obtained CR. In remission patients, 61% had 1-4/2000 positive cells (0.05-0.19%). Higher frequencies were found in two patients in early relapse and in one patient in early remission. However, a negative test did not exclude relapse. Since false positives were negligible and because most t(8;21) AMLs express CD34, we asked whether cell sorting combined with FISH would increase the sensitivity. In one patient, we observed that 80% of CD34+ cells were t(8;21)+ at 2 months from initial clinical and cytogenetic remission. However, by 5 months the pre- and post-sorted populations contained 0.15% and 0.06% t(8;21) cells, respectively. Whereas essentially all t(8;21) cells in the initial specimen expressed CD34, only 0.6% were subsequently CD34+. These results are consistent with in vitro assays showing that residual t(8;21) cells undergo differentiation. Thus, FISH can identify MRD in a majority of t(8;21) patients and, combined with CD34+ selection, may provide an indirect assessment of the differentiation state of residual t(8;21) cells. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
7. Low T-cell proportion in the tumor microenvironment is associated with immune escape and poor survival in diffuse large B-cell lymphoma.
- Author
-
Song JY, Nwangwu M, He TF, Zhang W, Meawad H, Bedell V, Murata-Collins J, Skrabek P, Nasr MR, Scott D, Godfrey J, Lee P, Chan WC, Weisenburger DD, Perry AM, and Herrera AF
- Subjects
- Humans, Prognosis, CD8-Positive T-Lymphocytes metabolism, T-Lymphocyte Subsets metabolism, Tumor Microenvironment genetics, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics
- Abstract
The tumor microenvironment (TME) is important in the pathogenesis and prognosis of lymphoma. Previous studies have demonstrated that features of the diffuse large B-cell lymphoma (DLBCL) TME can be associated with prognosis, but questions remain about the mechanisms underlying these TME features, and the interplay between tumor cells and the local TME. Therefore, we performed multispectral immunofluorescence (mIF) using two 6-color panels to interrogate the cellular proportions of T-cell subsets, macrophages, and natural killer cells in 57 cases of de novo DLBCL treated with R-CHOP chemotherapy. We found that very low CD3+ T-cell proportion and low CD4+PD1+ and CD8+PD1+ T cells have poor survival compared to those with a high T-cell proportion. Also, cases with concurrently low TIM3 and PD1 have a poor prognosis. This poor prognosis with low T-cell proportion was validated using immune deconvolution of gene expression profiling data from 351 cases of DLBCL and an additional cohort of 53 cases of DLBCL using routine immunohistochemistry. In addition, cases with loss of B2M, HLA I and/or HLA II protein expression on the tumor cells also had a low T-cell proportion, providing evidence that lack of these proteins allows for immune evasion. Overall, our results show that patients with DLBCL with a low T-cell proportion in the TME have a poor survival when treated with R-CHOP and exhibit mechanisms of immune escape.
- Published
- 2023
- Full Text
- View/download PDF
8. High-grade B-cell lymphoma with concurrent MYC rearrangement and 11q aberrations: clinicopathologic, cytogenetic, and molecular characterization of 4 cases.
- Author
-
Shestakova A, Shao L, Smith LB, Ryan R, Bedell V, Murata-Collins J, Zhang W, Perry AM, and Song JY
- Subjects
- Humans, Male, Adult, Female, In Situ Hybridization, Fluorescence, Chromosome Aberrations, Karyotyping, Proto-Oncogene Proteins c-myc genetics, Gene Rearrangement, Burkitt Lymphoma diagnosis, Burkitt Lymphoma genetics, Burkitt Lymphoma pathology, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
High-grade B-cell lymphoma with 11q aberrations (LBL-11q) resembles Burkitt lymphoma (BL), is negative for MYC rearrangement, and harbors chromosome 11q aberrations. Rare cases of high-grade B-cell lymphoma with concurrent MYC rearrangement and 11q aberrations (HGBCL-MYC-11q) have been described. In this study, we report the clinicopathologic, cytogenetic, and molecular findings in 4 such cases. Diagnoses were made on tissue or bone marrow biopsies. Karyotype, fluorescence in situ hybridization, genomic microarray analyses, and next-generation sequencing were performed. All patients were male (median age, 39 years). Three cases were diagnosed as BL, while one was diagnosed as diffuse large B-cell lymphoma. Karyotypes (available in 2 patients) were complex. In 1 patient, copy number analysis showed gains at 1q21.1-q44 and 13q31.3 and loss of 13q34, abnormalities typically seen in BL. All of our cases showed 2 or more mutations that are recurrent in BL, including ID3, TP53, DDX3X, CCND3, FBXO1, and MYC. Two cases showed a GNA13 mutation, commonly seen in LBL-11q. Cases of HGBCL-MYC-11q display overlapping morphologic and immunophenotypic, as well as cytogenetic and molecular features between BL and LBL-11q, with a mutational landscape enriched for mutations recurrent in BL. Concurrent MYC rearrangement with 11q abnormalities is important to recognize, especially as it has implications for their classification., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
9. Relative frequency and clinicopathologic characteristics of MYC-rearranged follicular lymphoma.
- Author
-
Chaudhary S, Brown N, Song JY, Yang L, Skrabek P, Nasr MR, Wong JT, Bedell V, Murata-Collins J, Kochan L, Li J, Zhang W, Chan WC, Weisenburger DD, and Perry AM
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor analysis, DNA Mutational Analysis, Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Lymphoma, Follicular chemistry, Lymphoma, Follicular drug therapy, Lymphoma, Follicular pathology, Male, Manitoba, Middle Aged, Mutation, Prognosis, Proto-Oncogene Proteins c-myc analysis, Tissue Array Analysis, United States, Biomarkers, Tumor genetics, Gene Rearrangement, Lymphoma, Follicular genetics, Proto-Oncogene Proteins c-myc genetics
- Abstract
MYC rearrangement is a relatively rare genetic abnormality in follicular lymphoma (FL). In this study, we evaluated the relative frequency of MYC rearrangement in 522 cases of FL and studied their clinicopathologic, cytogenetic, and molecular characteristics. Fluorescence in situ hybridization studies for MYC (break-apart probe), MYC/IGH, IGH/BCL2, and BCL6 rearrangements were performed on tissue microarrays. Immunohistochemical stains for CD10, BCL2, BCL6, and MYC were performed and scored on MYC-rearranged cases. On 4 FL cases, a custom targeted panel of 356 genes was used for mutation analysis. Ten cases (1.9%) were positive for MYC rearrangement. Histologically, 6 of 10 cases were grade 1-2, and 4 cases were grade 3A. By immunohistochemistry, 9 of 9 tested cases were CD10+, all cases were BCL6+, and 9/10 cases were BCL2+. MYC protein staining was low in all cases tested. IGH/BCL2 rearrangement was detected in 5 of 9 cases, whereas BCL6 rearrangement was detected in 3 of 7 tested cases and 4 of 10 cases showed MYC/IGH rearrangement. The most commonly detected mutations in the MYC-positive cases included HLA-B, TNFRSF14, and KMT2D. MYC and/or B2M abnormalities were detected in 2 cases. In conclusion, MYC rearrangement is uncommon in FL and these cases do not appear to have specific histologic characteristics. Molecular analysis showed abnormalities in genes associated with transformation, namely MYC and B2M. Larger studies are needed to evaluate if MYC-rearrangement in FL has prognostic significance., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
10. Quantitative Impact of the 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Practice Guideline Update on Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: A Systematic Analysis.
- Author
-
Wei CH, Garcia L, Murata-Collins J, Schmolze D, and Apple S
- Subjects
- Breast Neoplasms pathology, Humans, Predictive Value of Tests, Reproducibility of Results, Retrospective Studies, Biomarkers, Tumor genetics, Breast Neoplasms genetics, Immunohistochemistry standards, In Situ Hybridization, Fluorescence standards, Practice Guidelines as Topic standards, Receptor, ErbB-2 genetics
- Abstract
Context.—: The global impact of the new 2018 American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) practice guideline update on the overall HER2 status designation, compared with the prior 2013 iteration, is unknown., Objectives.—: To report the quantitative impact of the new guideline on HER2 status distribution., Design.—: The analysis comprised a retrospective cohort of patients from the authors' institution, combined with other peer-reviewed publications that assessed the impact of the 2018 guideline in relation to the 2013 guideline., Results.—: Our study revealed that the new guideline led to an average 9% reclassification rate for the overall HER2 status, with a net gain in overall HER2 negative designation. This is largely due to reclassification of the equivocal (Group 4) groups. Unexpectedly, infrequent but consistent discordance between Group 1/5 and fluorescence in situ hybridization results are observed across studies (1.8%; 73 of 3965 cases where fluorescence in situ hybridization and immunohistochemistry are both reported)., Conclusions.—: Early clinical recognition of these resultant changes, including emerging issues of tumor heterogeneity, and potential discordance between immunohistochemistry to fluorescence in situ hybridization, is important for accurate clinical assessment of individual HER2 test results.
- Published
- 2021
- Full Text
- View/download PDF
11. Validation of the Double-Hit Gene Expression Signature (DLBCL90) in an Independent Cohort of Patients with Diffuse Large B-Cell Lymphoma of Germinal Center Origin.
- Author
-
Nguyen H, Perry A, Skrabek P, Nasr M, Herrera AF, Bedell V, Murata-Collins J, Pillai R, Xu M, Chen L, Chan WC, Weisenburger DD, Scott DW, and Song JY
- Subjects
- Cohort Studies, Female, Follow-Up Studies, Gene Rearrangement, Germinal Center metabolism, Humans, In Situ Hybridization, Fluorescence, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics, Male, Middle Aged, Prognosis, Survival Rate, Translocation, Genetic, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor genetics, DNA Copy Number Variations, Germinal Center pathology, Lymphoma, Large B-Cell, Diffuse pathology, Mutation, Transcriptome
- Abstract
The prognosis of diffuse large B-cell lymphoma (DLBCL) has been associated with clinical parameters, cell of origin, and various genetic aberrations. Recently, a NanoString gene expression assay (DLBCL90) was developed, which identifies DLBCL cases with an outcome similar to those with double- or triple-hit DLBCL with both MYC and BCL2 rearrangements. This study validates the predictive ability of the DLBCL90 assay in an independent cohort of patients with the germinal center B-cell subtype DLBCL. A customized targeted sequencing panel was used to analyze the mutational profile in these patients. Cases with a double or triple hit by conventional fluorescence in situ hybridization cytogenetic analysis are known to have a poor prognosis, and the DLBCL90 gene expression signature identified these cases, as well as additional cases that would have otherwise been missed by fluorescence in situ hybridization analysis. Our findings validate use of the DLBCL90 assay for identifying high-risk patients for new and innovative therapies., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
12. Double-hit Signature with TP53 Abnormalities Predicts Poor Survival in Patients with Germinal Center Type Diffuse Large B-cell Lymphoma Treated with R-CHOP.
- Author
-
Song JY, Perry AM, Herrera AF, Chen L, Skrabek P, Nasr MR, Ottesen RA, Nikowitz J, Bedell V, Murata-Collins J, Li Y, McCarthy C, Pillai R, Wang J, Wu X, Zain J, Popplewell L, Kwak LW, Nademanee AP, Niland JC, Scott DW, Gong Q, Chan WC, and Weisenburger DD
- Subjects
- Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Female, Follow-Up Studies, Gene Expression Profiling, Germinal Center drug effects, Germinal Center metabolism, Humans, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse pathology, Male, Middle Aged, Prednisone administration & dosage, Prognosis, Retrospective Studies, Rituximab administration & dosage, Survival Rate, Translocation, Genetic, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor genetics, Germinal Center pathology, Lymphoma, Large B-Cell, Diffuse mortality, Mutation, Tumor Suppressor Protein p53 genetics
- Abstract
Purpose: We performed detailed genomic analysis on 87 cases of de novo diffuse large B-cell lymphoma of germinal center type (GCB DLBCL) to identify characteristics that are associated with survival in those treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)., Experimental Design: The cases were extensively characterized by combining the results of IHC, cell-of-origin gene expression profiling (GEP; NanoString), double-hit GEP (DLBCL90), FISH cytogenetic analysis for double/triple-hit lymphoma, copy-number analysis, and targeted deep sequencing using a custom mutation panel of 334 genes., Results: We identified four distinct biologic subgroups with different survivals, and with similarities to the genomic classifications from two large retrospective studies of DLBCL. Patients with the double-hit signature, but no abnormalities of TP53 , and those lacking EZH2 mutation and/or BCL2 translocation, had an excellent prognosis. However, patients with an EZB-like profile had an intermediate prognosis, whereas those with TP53 inactivation combined with the double-hit signature had an extremely poor prognosis. This latter finding was validated using two independent cohorts., Conclusions: We propose a practical schema to use genomic variables to risk-stratify patients with GCB DLBCL. This schema provides a promising new approach to identify high-risk patients for new and innovative therapies., (©2021 American Association for Cancer Research.)
- Published
- 2021
- Full Text
- View/download PDF
13. Genomic characterization of diffuse large B-cell lymphoma transformation of nodular lymphocyte-predominant Hodgkin lymphoma.
- Author
-
Song JY, Egan C, Bouska AC, Zhang W, Gong Q, Venkataraman G, Herrera AF, Chen L, Ottesen R, Niland JC, Bedell V, Valle-Catuna M, Murata-Collins J, Weisenburger DD, Iqbal J, Jaffe ES, and Chan WC
- Subjects
- Adolescent, Adult, Aged, Female, Gene Dosage, Genomics, Hodgkin Disease pathology, Humans, Immediate-Early Proteins genetics, Lymphoma, Large B-Cell, Diffuse pathology, Male, Middle Aged, Mutation, Protein Serine-Threonine Kinases genetics, Young Adult, Hodgkin Disease genetics, Lymph Nodes pathology, Lymphocytes pathology, Lymphoma, Large B-Cell, Diffuse genetics
- Published
- 2020
- Full Text
- View/download PDF
14. Long-Term Outcomes of Patients with Acute Myelogenous Leukemia Treated with Myeloablative Fractionated Total Body Irradiation TBI-Based Conditioning with a Tacrolimus- and Sirolimus-Based Graft-versus-Host Disease Prophylaxis Regimen: 6-Year Follow-Up from a Single Center.
- Author
-
Salhotra A, Hui S, Yang D, Mokhtari S, Mei M, Al Malki MM, Aldoss I, Ali H, Sandhu KS, Aribi A, Khaled S, Dandapani S, Peng K, Teh JB, Murata-Collins J, Budde E, Dadwal S, Pullarkat V, Snyder D, Spielberger R, Wong J, Armenian S, Marcucci G, Forman SJ, Nakamura R, and Stein A
- Subjects
- Adolescent, Adult, Busulfan therapeutic use, Cyclophosphamide therapeutic use, Follow-Up Studies, Humans, Middle Aged, Retrospective Studies, Sirolimus, Tacrolimus, Transplantation Conditioning, Whole-Body Irradiation, Young Adult, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy
- Abstract
Cyclophosphamide (Cy)/etoposide combined with fractionated total body irradiation (FTBI) or i.v. busulfan (Bu) has been the main conditioning regimens for allogeneic hematopoietic cell transplantation (alloHCT) for young patients with acute myelogenous leukemia (AML) eligible for a myeloablative conditioning (MAC) regimen. Recent data has suggested that i.v. Bu could be the preferred myeloablative regimen in patients with myeloid malignancies. However, Bu-based regimens are associated with higher rates of sinusoidal obstruction syndrome. Here we report long-term survival outcomes of patients with AML receiving FTBI combined with Cy or etoposide before undergoing alloHCT at City of Hope (COH). We obtained a retrospective review of a prospectively maintained institutional registry of clinical outcomes in 167 patients (median age, 41 years; range, 18 to 57 years) with AML in first or second complete remission who underwent alloHCT at COH between 2005 and 2015. Eligible patients received a MAC regimen with FTBI (1320 cGy) and Cy (120 mg/kg) for unrelated donor transplantation or etoposide (60 mg/kg) for related donor transplantation. Graft-versus-host disease (GVHD) prophylaxis was provided with tacrolimus and sirolimus. In this retrospective study, 6-year overall survival was 60% and nonrelapse mortality was 15%. The GRFS rate was 45% at 1 year and 39% at 2 years. We also describe late metabolic effects and report the cumulative incidence of secondary malignancies (9.5%). Overall, in this young adult patient population, our results compare favorably to chemotherapy-based (i.v. Bu) conditioning regimens without significant long-term toxicity arising from TBI-based regimens., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
15. Allogeneic Hematopoietic Cell Transplantation Outcomes in Patients Carrying Isocitrate Dehydrogenase Mutations.
- Author
-
Salhotra A, Afkhami M, Yang D, Mokhtari S, Telatar M, Gu D, Pillai RK, Weisenburger DD, Murata-Collins J, Weigel D, Aoun P, Aldoss I, Al Malki MM, Khaled S, Mei M, Ali H, Aribi A, Budde E, Sandhu K, O'Donnell M, Snyder D, Pullarkat V, Forman SJ, Marcucci G, Nakamura R, and Stein A
- Subjects
- Adult, Aged, Disease Management, Female, Genetic Predisposition to Disease, Humans, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Prognosis, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Isocitrate Dehydrogenase genetics, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy, Mutation
- Abstract
Background: Mutations in isocitrate dehydrogenase (IDH)1/2 genes result in nicotinamide adenine dinucleotide phosphate-dependent reduction of α-ketoglutarate and formation of 2-hydroxyglutarate, which blocks normal cellular differentiation and promotes leukemogenesis. Nearly 20% of acute myeloid leukemia (AML) patients carry IDH1/2 mutations. Although multiple investigators have described the prognostic implications of IDH mutations in AML patients receiving chemotherapy, the effect of these mutations on outcomes after allogeneic (allo) hematopoietic cell transplantation (HCT) is unknown., Patients and Methods: We report on the clinical outcome of a cohort of AML patients, who were tested for IDH mutations and underwent alloHCT at City of Hope (2015-2017). Of a total of 317 screened patients, 99 (31%) underwent alloHCT, of whom 23 carried and 76 did not carry IDH mutations (control)., Results: No statistical significance was detected in patient's overall survival (P = .84). With a median follow-up of 7.8 months, 1-year relapse rate of 29% and 13% was seen in the IDH-mutated and control group, respectively (P = .033). IDH1/2 mutation status remained significantly associated with relapse (hazard ratio, 2.8; P = .046) after inclusion of pre-HCT disease status in a multivariable model., Conclusion: Our results, despite low patient numbers, indicate that IDH mutations are associated with higher relapse rate after alloHCT. Further prospective studies on post transplantation IDH inhibition is required to improve outcomes in AML patients who carry IDH mutations., (Copyright © 2019. Published by Elsevier Inc.)
- Published
- 2019
- Full Text
- View/download PDF
16. Assessing genome-wide copy number aberrations and copy-neutral loss-of-heterozygosity as best practice: An evidence-based review from the Cancer Genomics Consortium working group for plasma cell disorders.
- Author
-
Pugh TJ, Fink JM, Lu X, Mathew S, Murata-Collins J, Willem P, and Fang M
- Subjects
- Biomarkers, Tumor genetics, Humans, In Situ Hybridization, Fluorescence, DNA Copy Number Variations, Evidence-Based Medicine, Loss of Heterozygosity, Neoplasms, Plasma Cell genetics
- Abstract
Background: Plasma cell neoplasms (PCNs) encompass a spectrum of disorders including monoclonal gammopathy of undetermined significance, smoldering myeloma, plasma cell myeloma, and plasma cell leukemia. Molecular subtypes have been defined by recurrent cytogenetic abnormalities and somatic mutations that are prognostic and predictive. Karyotype and fluorescence in situ hybridization (FISH) have historically been used to guide management; however, new technologies and markers raise the need to reassess current testing algorithms., Methods: We convened a panel of representatives from international clinical laboratories to capture current state-of-the-art testing from published reports and to put forward recommendations for cytogenomic testing of plasma cell neoplasms. We reviewed 65 papers applying FISH, chromosomal microarray (CMA), next-generation sequencing, and gene expression profiling for plasma cell neoplasm diagnosis and prognosis. We also performed a survey of our peers to capture current laboratory practice employed outside our working group., Results: Plasma cell enrichment is widely used prior to FISH testing, most commonly by magnetic bead selection. A variety of strategies for direct, short- and long-term cell culture are employed to ensure clonal representation for karyotyping. Testing of clinically-informative 1p/1q, del(13q) and del(17p) are common using karyotype, FISH and, increasingly, CMA testing. FISH for a variety of clinically-informative balanced IGH rearrangements is prevalent. Literature review found that CMA analysis can detect abnormalities in 85-100% of patients with PCNs; more specifically, in 5-53% (median 14%) of cases otherwise normal by FISH and cytogenetics. CMA results in plasma cell neoplasms are usually complex, with alteration counts ranging from 1 to 74 (median 10-20), primarily affecting loci not covered by FISH testing. Emerging biomarkers include structural alterations of MYC as well as somatic mutations of KRAS, NRAS, BRAF, and TP53. Together, these may be measured in a comprehensive manner by a combination of newer technologies including CMA and next-generation sequencing (NGS). Our survey suggests most laboratories have, or are soon to have, clinical CMA platforms, with a desire to move to NGS assays in the future., Conclusion: We present an overview of current practices in plasma cell neoplasm testing as well as an algorithm for integrated FISH and CMA testing to guide treatment of this disease., (Copyright © 2018. Published by Elsevier Inc.)
- Published
- 2018
- Full Text
- View/download PDF
17. Favorable impact of allogeneic stem cell transplantation in patients with therapy-related myelodysplasia regardless of TP53 mutational status.
- Author
-
Aldoss I, Pham A, Li SM, Gendzekhadze K, Afkhami M, Telatar M, Hong H, Padeganeh A, Bedell V, Cao T, Khaled SK, Malki MMA, Salhotra A, Ali H, Aribi A, Palmer J, Aoun P, Spielberger R, Stein AS, Snyder D, O'Donnell MR, Murata-Collins J, Senitzer D, Weisenburger D, Forman SJ, Pullarkat V, Marcucci G, Pillai R, and Nakamura R
- Subjects
- Female, Humans, Male, Middle Aged, Mutation, Myelodysplastic Syndromes chemically induced, Myelodysplastic Syndromes mortality, Transplantation, Homologous, Myelodysplastic Syndromes therapy, Stem Cell Transplantation methods, Tumor Suppressor Protein p53 genetics
- Abstract
Therapy-related myelodysplastic syndrome is a long-term complication of cancer treatment in patients receiving cytotoxic therapy, characterized by high-risk genetics and poor outcomes. Allogeneic hematopoietic cell transplantation is the only potential cure for this disease, but the prognostic impact of pre-transplant genetics and clinical features has not yet been fully characterized. We report here the genetic and clinical characteristics and outcomes of a relatively large cohort of patients with therapy-related myelodysplastic syndrome (n=67) who underwent allogeneic transplantation, comparing these patients to similarly treated patients with de novo disease (n=199). The 5-year overall survival was not different between patients with therapy-related and de novo disease (49.9% versus 53.9%; P =0.61) despite a higher proportion of individuals with an Intermediate-2/High International Prognostic Scoring System classification (59.7% versus 43.7%; P =0.003) and high-risk karyotypes (61.2% versus 30.7%; P<0.01) among the patients with therapy-related disease. In mutational analysis, TP53 alteration was the most common abnormality in patients with therapy-related disease (n=18: 30%). Interestingly, the presence of mutations in TP53 or in any other of the high-risk genes ( EZH2 , ETV6 , RUNX1 , ASXL1 : n=29: 48%) did not significantly affect either overall survival or relapse-free survival. Allogeneic stem-cell transplantation is, therefore, a curative treatment for patients with therapy-related myelodysplastic syndrome, conferring a similar long-term survival to that of patients with de novo disease despite higher-risk features. While TP53 alteration was the most common mutation in therapy-related myelodysplastic syndrome, the finding was not detrimental in our case-series., (Copyright© 2017 Ferrata Storti Foundation.)
- Published
- 2017
- Full Text
- View/download PDF
18. Cyclin D1 depletion induces DNA damage in mantle cell lymphoma lines.
- Author
-
Mohanty S, Mohanty A, Sandoval N, Tran T, Bedell V, Wu J, Scuto A, Murata-Collins J, Weisenburger DD, and Ngo VN
- Subjects
- Animals, Apoptosis genetics, Cell Cycle genetics, Cell Line, Tumor, Cell Survival genetics, DNA Replication, Disease Models, Animal, Heterografts, Humans, Lymphoma, Mantle-Cell pathology, Mice, Proto-Oncogene Mas, RNA Interference, RNA, Small Interfering genetics, Cyclin D1 metabolism, DNA Damage, Lymphoma, Mantle-Cell genetics, Lymphoma, Mantle-Cell metabolism
- Abstract
Elevated cyclin D1 (CCND1) expression levels in mantle cell lymphoma (MCL) are associated with aggressive clinical manifestations related to chemoresistance, but little is known about how this important proto-oncogene contributes to the resistance of MCL. Here, we showed that RNA interference-mediated depletion of CCND1 increased caspase-3 activities and induced apoptosis in the human MCL lines UPN-1 and JEKO-1. In vitro and xenotransplant studies revealed that the toxic effect of CCND1 depletion in MCL cells was likely due to increase in histone H2AX phosphorylation, a DNA damage marker. DNA fiber analysis suggested deregulated replication initiation after CCND1 depletion as a potential cause of DNA damage. Finally, in contrast to depletion or inhibition of cyclin-dependent kinase 4, CCND1 depletion increased chemosensitivity of MCL cells to replication inhibitors hydroxyurea and cytarabine. Our findings have an important implication for CCND1 as a potential therapeutic target in MCL patients who are refractory to standard chemotherapy.
- Published
- 2017
- Full Text
- View/download PDF
19. Philadelphia chromosome as a recurrent event among therapy-related acute leukemia.
- Author
-
Aldoss I, Stiller T, Song J, Al Malki M, Ali H, Salhotra A, Aribi A, Khaled S, Gaytan P, Murata-Collins J, Palmer J, Snyder D, O'Donnell M, Nakamura R, Stein AS, Forman SJ, Marcucci G, and Pullarkat V
- Subjects
- Combined Modality Therapy, Humans, Neoplasms, Second Primary mortality, Neoplasms, Second Primary therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Prognosis, Recurrence, Neoplasms, Second Primary diagnosis, Neoplasms, Second Primary etiology, Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma etiology
- Published
- 2017
- Full Text
- View/download PDF
20. Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation.
- Author
-
Herrera AF, Mei M, Low L, Kim HT, Griffin GK, Song JY, Merryman RW, Bedell V, Pak C, Sun H, Paris T, Stiller T, Brown JR, Budde LE, Chan WC, Chen R, Davids MS, Freedman AS, Fisher DC, Jacobsen ED, Jacobson CA, LaCasce AS, Murata-Collins J, Nademanee AP, Palmer JM, Pihan GA, Pillai R, Popplewell L, Siddiqi T, Sohani AR, Zain J, Rosen ST, Kwak LW, Weinstock DM, Forman SJ, Weisenburger DD, Kim Y, Rodig SJ, Krishnan A, and Armand P
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Disease-Free Survival, Female, Humans, Lymphoma, Large B-Cell, Diffuse chemistry, Male, Middle Aged, Proto-Oncogene Proteins c-bcl-2 analysis, Proto-Oncogene Proteins c-bcl-6 analysis, Proto-Oncogene Proteins c-myc analysis, Retrospective Studies, Survival Rate, Transplantation, Autologous, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse therapy, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-6 genetics, Proto-Oncogene Proteins c-myc genetics, Stem Cell Transplantation
- Abstract
Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.
- Published
- 2017
- Full Text
- View/download PDF
21. Burkitt leukemia limited to the bone marrow has a better prognosis than Burkitt lymphoma with bone marrow involvement in adults.
- Author
-
Song JY, Venkataraman G, Fedoriw Y, Herrera AF, Siddiqi T, Alikhan MB, Kim YS, Murata-Collins J, Weisenburger DD, Liu X, and Duffield AS
- Subjects
- Adult, Aged, Burkitt Lymphoma therapy, Combined Modality Therapy, Female, Humans, Karyotype, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Prognosis, Retrospective Studies, Treatment Outcome, Young Adult, Bone Marrow pathology, Burkitt Lymphoma mortality, Burkitt Lymphoma pathology
- Abstract
Burkitt lymphoma patients with bulky disease often have bone marrow involvement. However, leukemic presentation of Burkitt lymphoma in the absence of a mass (pure Burkitt leukemia; PBL) is uncommon. Both PBL and Burkitt lymphoma/leukemia, presenting with a tumor mass and marrow involvement (BLL), are considered stage IV disease, which is associated with a poor prognosis. However, there is limited information on the prognosis in adults with PBL because they have typically been included in cohorts of patients with BLL. This study identified 23 patients, which included 10 PBL and 13 BLL cases. Complex karyotypes (100%) were seen in all BLL cases compared to the PBL group (40%; p = 0.061). Patients with PBL had a significantly better 5-year overall survival of 87.5% vs only 24.3% in the BLL group (p = 0.005). The 5-year overall survival of patients with PBL treated with intensive chemotherapy is superior to those with BLL who are similarly treated.
- Published
- 2016
- Full Text
- View/download PDF
22. Extramedullary relapse following reduced intensity allogeneic hematopoietic cell transplant for adult acute myelogenous leukemia.
- Author
-
Kogut N, Tsai NC, Thomas SH, Palmer J, Paris T, Murata-Collins J, and Forman SJ
- Subjects
- Acute Disease, Adult, Aged, Female, Hematopoietic Stem Cell Transplantation methods, Humans, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Recurrence, Risk Assessment methods, Risk Assessment statistics & numerical data, Risk Factors, Survival Analysis, Transplantation, Homologous, Young Adult, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid surgery
- Published
- 2013
- Full Text
- View/download PDF
23. Late relapses following reduced intensity allogeneic transplantation in patients with multiple myeloma: a long-term follow-up study.
- Author
-
Sahebi F, Shen Y, Thomas SH, Rincon A, Murata-Collins J, Palmer J, Krishnan AY, Karanes C, Htut M, Somlo G, and Forman SJ
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation statistics & numerical data, Combined Modality Therapy, Female, Follow-Up Studies, Graft vs Host Disease epidemiology, Humans, Kaplan-Meier Estimate, Living Donors, Male, Melphalan administration & dosage, Middle Aged, Multiple Myeloma drug therapy, Multiple Myeloma genetics, Multiple Myeloma mortality, Proportional Hazards Models, Recurrence, Remission Induction, Retrospective Studies, Time Factors, Transplantation, Autologous, Transplantation, Homologous, Treatment Outcome, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Whole-Body Irradiation, Multiple Myeloma surgery, Peripheral Blood Stem Cell Transplantation statistics & numerical data, Transplantation Conditioning methods
- Abstract
We analysed the long-term outcomes of 60 multiple myeloma patients who underwent reduced intensity allogeneic stem cell transplantation between August 2000 and March 2008. Regimens included fludarabine and melphalan conditioning (flu-mel regimen) for allogeneic haematopoietic cell transplant (HCT) or a planned tandem regimen consisting of high-dose melphalan conditioning for autograft followed by low-dose total body irradiation conditioning for allogeneic HCT (auto-allo regimen). Donors included human-leucocyte-antigen-matched siblings (n = 55) or matched unrelated donors (n = 5). With a median follow-up of 9·8 years, 7-year overall survival (OS) and progression-free survival (PFS) were 60% and 31%, respectively. By multivariate Cox regression analysis, disease status of complete response (CR) or partial response (PR) at transplant and the presence of chronic graft-versus-host disease were significantly associated with improved OS. Only disease status was significantly associated with improved PFS. We noted a surprising number of very late relapses, with six patients (10%) relapsing between 6 and 12 years post-transplant. Among the six late relapse patients, all were transplanted within 14 months of diagnosis, five had normal karyotypes, and five were in CR/PR. Our data provide additional evidence that, while survival may be extended by reduced intensity allogeneic transplant, ultimately, it may not offer a cure., (© 2012 Blackwell Publishing Ltd.)
- Published
- 2013
- Full Text
- View/download PDF
24. Durable clinical, cytogenetic, and molecular remissions after allogeneic hematopoietic cell transplantation for refractory Sezary syndrome and mycosis fungoides.
- Author
-
Molina A, Zain J, Arber DA, Angelopolou M, O'Donnell M, Murata-Collins J, Forman SJ, and Nademanee A
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Busulfan administration & dosage, Cyclophosphamide administration & dosage, Female, Humans, Karyotyping, Male, Middle Aged, Mycosis Fungoides genetics, Mycosis Fungoides pathology, Retrospective Studies, Sezary Syndrome genetics, Sezary Syndrome pathology, Transplantation, Homologous, Treatment Outcome, Whole-Body Irradiation, Hematopoietic Stem Cell Transplantation, Mycosis Fungoides therapy, Sezary Syndrome therapy
- Abstract
Purpose: Sezary syndrome (SS) and tumor-stage mycosis fungoides (MF) are generally incurable with currently available treatments. We conducted a retrospective study to evaluate the outcome of allogeneic hematopoietic stem-cell transplantation (HSCT) in this patient population., Patient and Methods: From August 1996 through October 2002, eight patients with advanced MF/SS underwent allogeneic HSCT at our institution. All patients were heavily pretreated, having failed a median number of seven prior therapies (range, five to 12). Clonal T-cell populations in peripheral blood or bone marrow were detectable by polymerase chain reaction analyses of T-cell receptor gamma-chain gene rearrangements in six patients and cytogenetics in three patients. The conditioning regimen included total-body irradiation and cyclophosphamide (n = 3), busulfan and cyclophosphamide (n = 1), and the reduced-intensity regimen of fludarabine and melphalan (n = 4). Allogeneic hematopoietic stem cells were obtained from HLA-matched siblings (n = 4) and unrelated donors (n = 4)., Results: All patients achieved complete clinical remission and resolution of molecular and cytogenetic markers of disease within 30 to 60 days after HSCT. Two patients died from transplantation-related complications; graft-versus-host disease (GVHD; n = 1) and respiratory syncytial virus pneumonia (n = 1). With a median follow-up of 56 months, six patients remain alive and without evidence of lymphoma., Conclusion: Our results suggest that allogeneic HSCT from both HLA-matched sibling and unrelated donors can induce durable clinical, molecular, and cytogenetic remissions in patients with advanced cutaneous T-cell lymphoma that is refractory to standard therapies.
- Published
- 2005
- Full Text
- View/download PDF
25. Simultaneous detection of multiple genetic aberrations in single cells by spectral fluorescence in situ hybridization.
- Author
-
Slovak ML, Tcheurekdjian L, Zhang FF, and Murata-Collins JL
- Subjects
- Aneuploidy, Breast Neoplasms genetics, Breast Neoplasms pathology, Chromosome Deletion, Feasibility Studies, Female, Humans, Image Processing, Computer-Assisted, Lymphocytes ultrastructure, Male, Microscopy, Fluorescence methods, Neoplasm Recurrence, Local genetics, Neoplasm, Residual, Neoplasms pathology, Pilot Projects, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Reproducibility of Results, Sensitivity and Specificity, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms pathology, Chromosome Aberrations, In Situ Hybridization, Fluorescence methods, Neoplasms genetics
- Abstract
Spectral fluorescence in situ hybridization (S-FISH) is a novel molecular cytogenetic approach that detects multiple disease-specific chromosomal aberrations in interphase nuclei using combinatorial fluorescence and digital imaging microscopy. A panel of six centromeric probes for chromosomes 7, 8, 9, 10, X, and Y, using a unique two-dye combination of four fluorophores, was developed to assess ploidy in breast tumors, bladder washings, and leukemia. Validation of S-FISH was performed by classic cytogenetics when metaphases were available or by standard fluorescence in situ hybridization (FISH) analyses. S-FISH identified clonal aberrations in newly diagnosed breast tumors and recurrent bladder cancer and revealed minimal residual disease in hyperdiploid acute lymphocytic leukemia, providing "proof of concept." Like standard FISH, aberrations were identified in poor growth/no growth specimen at the single cell level; however, S-FISH provided increased sensitivity over standard FISH by surveying six genetic targets instead of one or two. Disadvantages of the current assay include labor intensive screening and interpretative challenges with signal overlap in highly aneuploid samples and focal plane distortions. S-FISH appears to be a sensitive oncology assay with significant clinical application for early detection of new or reemerging clones, allowing for earlier therapeutic intervention and development of probe panels for individualized therapy.
- Published
- 2001
26. Twenty-four-color spectral karyotyping reveals chromosome aberrations in cytogenetically normal acute myeloid leukemia.
- Author
-
Zhang FF, Murata-Collins JL, Gaytan P, Forman SJ, Kopecky KJ, Willman CL, Appelbaum FR, and Slovak ML
- Subjects
- Acute Disease, Chromosome Banding standards, Female, Humans, In Situ Hybridization, Fluorescence, Leukemia, Myeloid diagnosis, Male, Middle Aged, Reproducibility of Results, Staining and Labeling standards, Chromosome Aberrations genetics, Karyotyping methods, Leukemia, Myeloid genetics, Staining and Labeling methods
- Abstract
Multicolor spectral karyotyping allows simultaneous visualization of all human chromosomes and screening for chromosomal rearrangements without a priori knowledge of any abnormalities involved. Based on this potentially increased sensitivity, we investigated, in a preliminary manner, whether spectral karyotyping could detect cytogenetic aberrations in karyotypically normal leukemia. The test population was comprised of 28 cryopreserved, cytogenetically normal acute myeloid leukemia (AML) samples from patients registered to a randomized trial for previously untreated AML (SWOG 9031). Two normal and 12 samples with known cytogenetic aberrations were used to validate and establish the diagnostic accuracy of the spectral karyotyping assay and instrumentation in a clinical setting. Enumeration and region-specific DNA fluorescence in situ hybridization (FISH) probes verified discrepant results. In the validation data set, spectral karyotyping refined complex karyotypic rearrangements in six cases and defined the chromosomal origin of a "jumping" homogeneously staining region; however, the technology was less sensitive in the detection of subtelomeric rearrangements and double minute chromosomes. In the test population, spectral karyotyping identified previously undetected cytogenetic aberrations in two cases (7%) of karyotypically normal AML: a cryptic 11q23 translocation in 20/20 cells and a minor monosomy 7 clone in 3/21 cells (FISH, 10.5%). Both of these abnormalities are considered to confer a poor prognosis when based on classical cytogenetic prognostic criteria. As an adjunct to classical cytogenetics and standard FISH analyses, the additive resolution of spectral karyotyping, in particular, with chromosome paints spiked with subtelomeric and/or locus-specific probes, may allow significant gains to be made in diagnostic accuracy and recognition of genotype/phenotype prognostic relationships, and in defining underlying biologic mechanisms in cancer. Genes Chromosomes Cancer 28:318-328, 2000., (Copyright 2000 Wiley-Liss, Inc.)
- Published
- 2000
- Full Text
- View/download PDF
27. Ticlopidine-induced aplastic anemia: development of chromosomal abnormalities and response to immunosuppressive therapy.
- Author
-
Pullarkat VA, Rho H, Murata-Collins JL, and Liebman HA
- Subjects
- Aged, Aged, 80 and over, Anemia, Aplastic genetics, Chromosome Disorders, Cyclosporine therapeutic use, Dexamethasone therapeutic use, Fibrinolytic Agents adverse effects, Humans, Male, Platelet Aggregation Inhibitors adverse effects, Treatment Outcome, Anemia, Aplastic chemically induced, Anemia, Aplastic drug therapy, Bone Marrow drug effects, Chromosome Aberrations chemically induced, Chromosome Aberrations drug therapy, Immunosuppressive Agents therapeutic use, Ticlopidine adverse effects
- Abstract
Severe aplastic anemia is a well-recognized complication of ticlopidine therapy that carries a high mortality. Therapy with colony-stimulating factors or corticosteroids has been largely ineffective in this disorder. We report a case of ticlopidine-induced aplastic anemia that was successfully treated with cyclosporine and high-dose dexamethasone. The patient rapidly responded to immunosuppressive therapy and had a normal hemogram after cessation of immunosuppression. On long-term follow-up, the patient developed a progressive macrocytic anemia. Repeat bone marrow evaluation demonstrated myelodysplasia with erythroid hypoplasia. An associated chromosomal abnormality consisting of a t(3;16) (q21; p13.3) translocation was detected. This is the first report of a chromosomal abnormality associated with ticlopidine induced marrow aplastic anemia., (Copyright 2000 Wiley-Liss, Inc.)
- Published
- 2000
- Full Text
- View/download PDF
28. Acute lymphoblastic leukemia. Survey of immunophenotype, French-American-British classification, frequency of myeloid antigen expression, and karyotypic abnormalities in 210 pediatric and adult cases.
- Author
-
Khalidi HS, Chang KL, Medeiros LJ, Brynes RK, Slovak ML, Murata-Collins JL, and Arber DA
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, France, Humans, Infant, Male, Middle Aged, Recurrence, United Kingdom, United States, Antigens, Differentiation, Myelomonocytic analysis, Chromosome Aberrations, Immunophenotyping, Karyotyping, Precursor Cell Lymphoblastic Leukemia-Lymphoma classification, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology
- Abstract
Immunophenotypic studies are essential to distinguish acute lymphoblastic leukemia (ALL) from minimally differentiated acute myeloid leukemia (AMLM0) and to classify ALL into immunologic subtypes. Frequently, immunophenotyping identifies myeloid antigen expression in ALL, causing a potential diagnostic problem. To evaluate the immunophenotype of ALL, we studied 210 cases of pediatric and adult ALL by flow cytometry and compared the results with the French-American-British (FAB) Cooperative Group classification and the karyotypic findings. Myeloid-associated antigens were expressed in 78 (45.6%) of precursor B-cell ALL cases. Pediatric precursor B ALLs had a higher frequency of myeloid antigen expression than did adult cases. All mature B-cell ALL cases were negative for TdT and myeloid antigens. Myeloid antigen expression was less frequent in T-cell ALL cases compared with precursor B-cell ALL cases. Of the 192 cases submitted for cytogenetic analysis, 147 were abnormal. The most common chromosomal translocation was the Philadelphia chromosome, which was more likely to have L2 blast morphology and a precursor B immunophenotype. Myeloid antigen expression was present in 70.8% of Ph-positive cases (P = .008). Chromosome rearrangements involving 11q23 also showed an increased frequency of myeloid antigen expression. Chromosome translocations involving regions of T-cell receptor genes were present in 24% of T-cell ALL cases. A high percentage of ALL cases, however, had various other cytogenetic abnormalities, many of which involved less well-studied chromosomal regions.
- Published
- 1999
- Full Text
- View/download PDF
29. Surface immunoglobulin light chain-positive acute lymphoblastic leukemia of FAB L1 or L2 type: a report of 6 cases in adults.
- Author
-
Vasef MA, Brynes RK, Murata-Collins JL, Arber DA, and Medeiros LJ
- Subjects
- Adolescent, Adult, Female, Follow-Up Studies, Humans, Immunohistochemistry, Immunophenotyping, Karyotyping, Male, Polymerase Chain Reaction, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Surface Properties, Immunoglobulin Light Chains metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism
- Abstract
Acute lymphoblastic leukemia (ALL) of B-cell lineage may be classified using the French-American-British (FAB) classification as L1, L2, or L3 type. L1 and L2 ALLs characteristically express terminal deoxynucleotidyl transferase (TdT) and are surface immunoglobulin (sIg)-negative. In contrast, L3 ALL is typically TdT-negative and sIg-positive. However, in a few large studies of children with ALL, sIg expression has been reported in less than 2% of L1 and L2 neoplasms. In these sIg-positive cases, IgM usually has been detected, with Ig light chain in a subset of tumors. Surface Ig expression in L1 or L2 ALL in adults is extremely rare; we found only 1 case report in the English literature. We report 6 cases of L1 or L2 ALL with an unusual immunophenotype arising in adults. In each tumor, the neoplastic cells expressed monotypic sIg light chain (4 lambda, 2 kappa) and TdT. Three tumors expressed CD34. Cytogenetic studies in 4 cases at diagnosis or relapse revealed no evidence of chromosomal translocations involving the c-myc locus, such as the t(8;14), t(2;8), or t(8;22). Three patients responded completely to chemotherapy and are alive; follow-up ranges from 18 to 57 months. Three patients died at 3, 13, and 14 months after diagnosis.
- Published
- 1998
- Full Text
- View/download PDF
30. Trisomy 14 in myelodysplastic syndromes: report of two cases and review of the literature.
- Author
-
Vasef MA, Murata-Collins JL, Alsabeh R, and Medeiros LJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Anemia, Refractory blood, Anemia, Refractory pathology, Blood Cell Count, Bone Marrow pathology, Erythrocytes pathology, Female, Humans, In Situ Hybridization, Fluorescence, Leukemia, Myelomonocytic, Chronic complications, Leukemia, Myelomonocytic, Chronic pathology, Male, Megakaryocytes pathology, Middle Aged, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes pathology, Syndrome, Anemia, Refractory genetics, Chromosomes, Human, Pair 14, Leukemia, Myelomonocytic, Chronic genetics, Myelodysplastic Syndromes genetics, Trisomy
- Abstract
Objective: To describe the pathologic features of two cases of myelodysplastic syndrome associated with trisomy 14 and to summarize the relevant literature., Results: In both cases, trisomy 14 was identified using conventional cytogenetic and fluorescence in situ hybridization methods. The patients were elderly men, 70 and 77 years old, who presented with anemia and thrombocytopenia. According to the French-American-British classification, case 1 was classified as refractory anemia with ringed sideroblasts, and case 2 was classified as chronic myelomonocytic leukemia. In both cases, the aspirate smears revealed obvious abnormalities in erythroid and megakaryocytic maturation, with more subtle abnormalities in myeloid maturation. The biopsy sections were hypercellular, and there was marked myeloid hyperplasia in case 2. Both patients received only supportive therapy after the diagnosis was established. Clinical follow-up was available for both patients. The patient in case 1 died 67 months after disease onset of an unrelated illness, and the patient in case 2 was alive at last follow-up, 12 months after diagnosis., Literature Review: Thirty-five cases of trisomy 14 have been previously reported in the literature, predominantly in cytogenetics journals, and the description of the pathologic findings for the majority of these cases is limited or not provided. According to published data, the majority of these cases are myelodysplastic syndromes or acute myeloid leukemias associated with myelodysplasia., Conclusions: The detection of trisomy 14 in the bone marrow strongly correlates with the presence of a myelodysplastic syndrome. The two cases of myelodysplastic syndrome associated with trisomy 14 we describe here did not exhibit characteristic morphologic findings that might suggest the presence of the cytogenetic abnormality.
- Published
- 1998
31. Fetal cells in maternal blood: recovery by charge flow separation.
- Author
-
Wachtel SS, Sammons D, Manley M, Wachtel G, Twitty G, Utermohlen J, Phillips OP, Shulman LP, Taron DJ, Müller UR, Koeppen P, Ruffalo TM, Addis K, Porreco R, Murata-Collins J, Parker NB, and McGavran L
- Subjects
- Chromosomes, Human, Pair 18, Down Syndrome diagnosis, Down Syndrome genetics, Erythrocytes, Female, Humans, In Situ Hybridization, Fluorescence, Male, Prenatal Diagnosis, Trisomy, Y Chromosome genetics, Cell Separation methods, Fetal Blood cytology, Pregnancy blood
- Abstract
Fetal blood cells can be recovered from the maternal circulation by charge flow separation (CFS), a method that obviates the risks associated with amniocentesis and chorionic villus sampling. By CFS, we processed blood samples from 13 women carrying male fetuses, 2 carrying fetuses with trisomy 21, and 1 who had delivered a stillborn infant with trisomy 18. On average more than 2000 fetal nucleated red blood cells were recovered per 20-ml sample of maternal blood. Recovery of fetal cells was confirmed by fluorescence in situ hybridization with probes for chromosomes Y, 18 and 21. After culturing of CFS-processed cells, amplification by the polymerase chain reaction revealed Y-chromosomal DNA in clones from four of six women bearing male fetuses, but not in clones from three women bearing female fetuses.
- Published
- 1996
- Full Text
- View/download PDF
32. Natural size classes in DNA from Chinese hamster metaphase chromosomes.
- Author
-
Murata-Collins JL and Clark RW
- Subjects
- Animals, Cell Line, Cricetinae, Cricetulus, Female, Hydrogen-Ion Concentration, Metaphase, Molecular Weight, Ovary, Chromosomes analysis, DNA isolation & purification
- Abstract
DNA from isolated Chinese hamster ovary (CHO) metaphase chromosomes can be obtained in three different molecular weight classes. The two largest forms have sedimentation coefficients of 80 and 120 S at 7,500 rpm. Based on sedimentation and speed dependence analysis these have molecular weights of 220 million and above 5,000 million, and are thought to be analogs of DNA classes observed in a prior study of human metaphase chromosomes. An extract can be converted to primarily the 80 S form through alkaline pH treatment of metaphase DNA. The third class (45 S DNA) is formed as a result of metaphase chromosome exposure to the nuclease Bal31, and has a mass distribution analogous to the CHO replicon.
- Published
- 1987
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.