21 results on '"Hussaini MO"'
Search Results
2. Clonotypic VDJ Rearrangements in Mixed Phenotype Acute Leukemia can be Successfully Utilized to Track Minimal Residual Disease.
- Author
-
Hennawi M, Quadeer F, Pakasticali N, Osman S, Tashkandi H, and Hussaini MO
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Aged, Phenotype, V(D)J Recombination, Neoplasm, Residual, High-Throughput Nucleotide Sequencing
- Abstract
Introduction: Multiplex polymerase chain reaction (PCR) and next-generation sequencing (NGS) can both be used to identify a neoplastic clonotype by targeting CDR3 and assessing rearrangements in IgH, IgK, IgL, TCR-β, and TCR-gamma loci. The clonotypic sequence can be robustly used to track minimal residual disease (MRD). The ability to track MRD by NGS in mixed phenotype acute leukemia (MPAL) is unknown and warrants investigation., Methods: Institutional Review Board (IRB) approval was obtained. Central Moffitt Cancer Center (MCC) database was searched to locate any patients with MPAL from over 600,000 entries. Patient charts were manually curated to identify those with clonoSEQ data, and clinical data was procured from the electronic medical record (EMR)., Results: Twenty-nine patients with MPAL were identified. Only 2 patients with clonoSEQ testing were found. Both demonstrated a B/myeloid phenotype, and both were bilineal. NGS (clonoSEQ) identified 4 dominant (IGH) (patient A; 8/2019) and 2 dominant sequences (patient B; 10/2019), respectively. In both patients, clonoSEQ testing successfully tracked minimal residual disease and mirrored clinical disease burden., Conclusions: This report is the first to confirm the utility of NGS-based MRD tracking in patients with MPAL and shows increased sensitivity of NGS over MRD flow cytometry., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
3. Drivers of deep molecular response and long-term outcomes in patients with core binding factor acute myeloid leukemia.
- Author
-
Patel PC, Ball S, Jain AG, Wang C, Hussaini MO, Aguirre LE, Chan O, Yun S, Kuykendall A, Padron E, Sweet K, Lancet JE, Komrokji RS, and Sallman DA
- Subjects
- Humans, Stem Cell Transplantation, Core Binding Factors genetics, Retrospective Studies, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute etiology
- Abstract
A swimmer plot on clinical course of patients undergoing allogeneic stem cell transplant for core binding factor acute myeloid leukemia., (© 2023 Wiley Periodicals LLC.)
- Published
- 2023
- Full Text
- View/download PDF
4. Sclerotic marginal zone lymphoma: A case report.
- Author
-
Moureiden Z, Tashkandi H, and Hussaini MO
- Abstract
Background: Marginal zone lymphoma (MZL) is an indolent non-Hodgkin B cell lymphoma with various architectural pattern including perifollicular, follicular colonization, nodular, micronodular, and diffuse patterns. A sclerotic variant has not been previously reported and represents a diagnostic pitfall., Case Summary: A 66-year-old male developed left upper extremity swelling. Chest computed tomography (CT) in September 2020 showed 14 cm mass in left axilla. Needle core biopsy of axillary lymph node showed sclerotic tissue with atypical B lymphoid infiltrate but was non-diagnostic. Excisional biopsy was performed for diagnosis and showed extensive fibrosis and minor component of infiltrating B cells. Flow cytometry showed a small population of CD5-, CD10-, kappa restricted B cells. Monoclonal immunoglobulin heavy chain and light chain gene rearrangement were identified. Upon being diagnosed with MZL, patient was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone and achieved complete remission by positron emission tomography/CT., Conclusion: This is an important case report because by morphology this case could have easily been overlooked as non-specific fibrosis with chronic inflammation representing a significant diagnostic pitfall. Moreover, this constitutes a new architectural pattern. While sclerotic lymphomas have rarely been described (often misdiagnosed as retroperitoneal fibrosis), we do not know of any cases describing this architectural presentation of MZL., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
5. Sex Disparities in Myelodysplastic Syndromes: Genotype, Phenotype, and Outcomes.
- Author
-
Tinsley-Vance SM, Ali NA, Ball S, Aguirre LE, Jain AG, Hussaini MO, Chan O, Kuykendall A, Sweet K, Lancet J, Padron E, Sallman DA, and Komrokji RS
- Subjects
- Male, Humans, Female, Prognosis, Splicing Factor U2AF genetics, Retrospective Studies, Mutation, Genotype, Phenotype, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes drug therapy
- Abstract
Introduction/Background The impact of biological sex on the clinical phenotype, genotype, and outcomes among patients with MDS is not well characterized. Materials and Methods We retrospectively reviewed the clinical and genomic data from male and female patients included in our institutional MDS database at Moffitt Cancer Center. Results Among 4580 patients with MDS, 2922 (66%) were men and 1658 (34%) were women. Women were younger (mean age 66.5 vs. 69 years for men, P < .001) at diagnosis. There were more Hispanic/black women than men (9% vs. 5%, P =<.001). Women had lower hemoglobin and higher platelet counts than men. More women had del 5q/monosomy 5 abnormalities compared to men (P =<.001). Therapy related MDS were more common in women than men (25% vs.17%, P=<.001). On assessment of molecular profile, SRSF2, U2AF1, ASXL1, and RUNX1 mutations were more frequent in men. The median overall survival (mOS) was 37.5 months (mo) for females compared to 35 monthsfor males, (P = .002). The mOS was significantly prolonged for women in lower-risk MDS, but not in higher-risk MDS. Women were more likely to respond to immunosuppression with ATG/CSA than men (38% vs. 19%, P= 0.04).Conclusion Ongoing research is needed for understanding the impact of sex on phenotype, genotype, and outcomes in patients diagnosed with MDS., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
6. Clinical characteristics and outcomes of EZH2-mutant myelodysplastic syndrome: A large single institution analysis of 1774 patients.
- Author
-
Ball S, Aguirre LE, Jain AG, Ali NA, Tinsley SM, Chan O, Kuykendall AT, Sweet K, Lancet JE, Sallman DA, Hussaini MO, Padron E, and Komrokji RS
- Subjects
- Humans, Aged, Prognosis, Retrospective Studies, Chromosome Aberrations, Mutation, Transcription Factors genetics, Enhancer of Zeste Homolog 2 Protein genetics, Myelodysplastic Syndromes therapy, Myeloproliferative Disorders
- Abstract
EZH2 mutations in myeloid neoplasms are loss of function type, and have been linked to poor overall survival (OS) in patients with myelodysplastic syndrome (MDS). However, the specific determinants of outcomes in EZH2-mutant (mut) MDS are not well characterized. In this single-center retrospective study, clinical and genomic data were collected on 1774 patients with MDS treated at Moffitt Cancer Center. In our cohort, 83 (4.7%) patients had a pathogenic EZH2 mutation. Patients with EZH2mut MDS were older than EZH2-wild type (wt) group (median age- 72 vs. 69 years, p = 0.010). The most common co-occurring mutation in EZH2mut MDS was ASXL1, with a significantly higher frequency than EZH2wt (54% vs. 19%, p < 0.001). Patients with EZH2mut MDS had lower response rates to hypomethylating agents compared to EZH2wt MDS (26% vs. 39%; p = 0.050). Median OS of patients with EZH2mut MDS was 30.8 months, with a significantly worse OS than EZH2wt group (35.5 vs. 61.2 months, p = 0.003) in the lower-risk IPSS-R categories. Among patients with EZH2mut MDS, co-presence of ASXL1 or RUNX1 mutations was associated with inferior median OS compared to their wt counterparts (26.8 vs. 48.7 months, p = 0.031). Concurrent chromosome 7 abnormalities (12%) were also associated with significantly worse OS (median OS- 20.8 vs. 35.5 months, p = 0.002) in EZH2mut MDS. Future clinical trials should explore the potential role of novel targeted therapies in improving outcomes in patients with EZH2mut MDS., Competing Interests: Conflict of Interest: Hussaini Consultancy/Advisory Board/Speaking for Adaptive Biotechnologies, Amgen, Aptitude Health, Bluprint Oncology, Celgene, Decibio, Diaceutics, Guidepoint, Seattle Genetics, Stemline, Tegus, Janssen. Tinsley-Vance: Jazz: Consultancy, Speakers Bureau; Taiho: Consultancy; Abbvie: Honoraria; Astellas: Speakers Bureau; Celgene/BMS: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy; Fresenius Kabi: Consultancy. Kuykendall: BluePrint Medicines: Honoraria, Research Funding, Speakers Bureau; Celgene/BMS: Honoraria, Research Funding, Speakers Bureau; CTI Biopharma: Honoraria; Incyte: Consultancy; Novartis: Honoraria, Speakers Bureau; PharmaEssentia: Honoraria; Prelude: Research Funding; Abbvie: Honoraria; Protagonist: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sweet: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. Lancet: AbbVie: Consultancy; Millennium Pharma/Takeda: Consultancy; Daiichi Sankyo: Consultancy; BerGenBio: Consultancy; ElevateBio Management: Consultancy; Astellas: Consultancy; Agios: Consultancy; Celgene/BMS: Consultancy; Jazz: Consultancy. Sallman: Takeda: Consultancy; Agios: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Intellia: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Aprea: Membership on an entity's Board of Directors or advisory committees, Research Funding; Magenta: Consultancy. Padron: Blueprint: Honoraria; Taiho: Honoraria; Incyte: Research Funding; BMS: Research Funding; Stemline: Honoraria; Kura: Research Funding. Komrokji: Taiho Oncology: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy; AbbVie: Consultancy; Acceleron: Consultancy; Jazz: Consultancy, Speakers Bureau; BMSCelgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ball, Aguirre, Jain, Ali, Chan, and Padron: No conflict of interest to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
7. Molecular annotation of extramedullary acute myeloid leukemia identifies high prevalence of targetable mutations.
- Author
-
Ball S, Knepper TC, Deutsch YE, Samra W, Watts JM, Bradley TJ, Chan O, Hussaini MO, Zhang L, Sweet KL, Kuykendall AT, Talati C, Padron E, Komrokji RS, Lancet JE, and Sallman DA
- Subjects
- Humans, Middle Aged, Mutation, Nucleophosmin, Prevalence, Prognosis, Retrospective Studies, Isocitrate Dehydrogenase genetics, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute epidemiology, Leukemia, Myeloid, Acute genetics
- Abstract
Background: Genomic landscape of extramedullary acute myeloid leukemia (EM-AML), including myeloid sarcoma (MS) and leukemia cutis (LC), is not well characterized. The potential utility of next-generation sequencing (NGS) using EM tissue is not established., Methods: In this multicenter retrospective study, clinical and NGS data were collected on patients with EM-AML. All statistical analyses were performed in SPSS Statistics (v 26)., Results: Our study included 58 patients with EM-AML. The median age at diagnosis was 62 years; 59% of patients had MS and 33% had LC. EM-AML was isolated (i.e., without blood or marrow involvement) in 31% and was first noted at relapse in 60% of patients. Median overall survival in our cohort was 18.2 months overall, with 19.1 months and 11.6 months in the newly diagnosed and the relapsed/refractory patients, respectively. At least one targetable or potentially targetable alteration was present in 52% of patients with EM-site NGS, with 26% IDH1, 21% NPM1, 11% IDH2, 6% FLT3, and 13% KMT2A-PTD. Mutations in IDH1 were significantly more prevalent on NGS from EM tissue than non-EM (blood or marrow) samples (26% vs. 3%; p = .030). Three of four patients treated with IDH inhibitors based on EM-site NGS experienced a complete response., Conclusions: Targetable mutations are frequent in EM-AML and EM-site NGS is warranted for selecting potential targeted therapies for patients with EM-AML., (© 2022 American Cancer Society.)
- Published
- 2022
- Full Text
- View/download PDF
8. Assessment of Clonotypic Rearrangements and Minimal Residual Disease in Lymphoid Malignancies.
- Author
-
Hussaini MO, Srivastava J, Lee LW, Nishihori T, Shah BD, Alsina M, Pinilla-Ibarz J, and Shain KH
- Subjects
- High-Throughput Nucleotide Sequencing methods, Humans, Neoplasm, Residual diagnosis, Neoplasm, Residual genetics, Receptors, Antigen, T-Cell genetics, Gene Rearrangement, Neoplasms, Plasma Cell
- Abstract
Context.—: Measurable (minimal) residual disease (MRD) is an independent prognostic factor for survival outcomes in patients with lymphoid and plasma cell malignancies and has been incorporated into consensus criteria regarding treatment response, strategy, and clinical trial endpoints. clonoSEQ (a next-generation sequencing [NGS]-MRD assay) uses multiplex polymerase chain reaction and NGS to identify clonotypic rearrangements at the immunoglobulin (Ig) H, IgK, IgL, T-cell receptor (TCR)-β, and TCR-γ loci, as well as translocated B-cell lymphoma 1/IgH and 2/IgH sequences for MRD assessment. Additionally, it can be used to confirm diagnoses of cutaneous T-cell lymphoma (CTCL)., Objective.—: To review the technical aspects of our experience using the clonoSEQ Assay in routine clinical practice., Design.—: In this single-center experience, 390 patients with lymphoid and plasma cell malignancies were assessed with the NGS-MRD Assay at a central laboratory., Results.—: Median time from arrival of the shipment to initiation of the assay (defined as captured in Adaptive's secure tracking system) was 2.1 hours. Overall, 317 patients had 1 or more samples submitted for sequence identification. Of these, 290 (91.5%) had trackable sequences identified. The median calibration rate of samples by malignancy (where n ≥ 10 samples, excluding CTCL samples) was 88.1%, across a variety of fresh and archived sample sources (177 of 201 samples). TCR-β and/or TCR-γ clonotypes were identified in 40 of 95 samples (42.1%) from 66 patients with suspected CTCL., Conclusions.—: This NGS-MRD Assay is a valuable and sensitive tool for monitoring MRD in patients with plasma cell and lymphoid malignancies and assisting in the diagnosis of CTCL., Competing Interests: Hussaini declares participating on advisory councils or committees for, and receiving honoraria from, Adaptive Biotechnologies Corp and consulting fees from Amgen. Srivastava and Lee are employees of, and hold stocks/shares with, Adaptive Biotechnologies Corp. Shah declares participating on advisory councils or committees for Adaptive Biotechnologies Corp. Pinilla-Ibarz declares receipt of honoraria from Adaptive Biotechnologies Corp. Shain declares receiving honoraria from Amgen, Inc, and consulting fees from Adaptive Biotechnologies Corp. Alsina has no relevant financial interest in the products or companies described in this article.
- Published
- 2022
- Full Text
- View/download PDF
9. Acquisition of IDH2 mutations in relapsed/refractory AML is associated with worse patient outcomes.
- Author
-
Song A, Altabbakh O, Sallman DA, Padron E, Talati C, and Hussaini MO
- Subjects
- Female, Humans, Male, Middle Aged, Prognosis, Recurrence, Remission Induction, Isocitrate Dehydrogenase genetics, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Mutation
- Abstract
Objectives: The presence of targeted therapy, Enasidenib, for IDH2-mutated AML underscores the importance of understanding the clonal dynamics of IDH2 mutations, which has not been elucidated. In the largest study of IDH2 clonal dynamics, we detail the IDH2-evolutionary patterns and their clinical significance., Methods: We analyzed ~6000 patients with NGS results to identify 120 AML patients with IDH2 mutations and longitudinal NGS testing. IDH2 mutation status was recorded at diagnosis, remission, relapse, and persistent disease., Results: One hundred and five patients were IDH2-positive at the initial diagnosis, and 15 acquired the mutation later. Of those 15 patients, 7 patients gained the mutation during persistent disease, 6 during relapse, and 2 at remission. Twenty-one patients (18%) who were IDH2-positive in a prior test remained IDH2-positive in remission. Twenty-four patients with IDH2-positive AML were IDH2-positive at relapse. IDH2-positive at diagnosis had better survival than IDH2 mutation acquired later in disease (P = .024). Patients who were IDH2-negative in remission had significantly improved survival (P = .002). Also, loss-of-IDH2 mutation with persistent disease had better OS (P = .035)., Conclusions: There are 70% that clear IDH2 in disease remission. 12% gain IDH2 mutation later, usually in the setting of refractory/relapsed AML. These patients fared worse. Longitudinal IDH2 testing may be helpful in prognostic stratification., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
10. Post-transplant relapse of therapy-related MDS as gastric myeloid sarcoma: Case report and review of literature.
- Author
-
Song A, Ghayouri M, Hiya F, and Hussaini MO
- Abstract
Introduction: Myelodysplastic syndrome (MDS) are hematologic neoplasms characterized by morphologic dysplasia and ineffective hematopoiesis in the bone marrow. The only potentially curative therapy is stem cell transplant. However, relapse remains a major challenge and is seen in about 25-40% of cases. Myeloid sarcoma presenting as relapse post allogeneic transplant for myeloid neoplasms is rare. We report the sentinel case of a patient with MDS who relapsed as gastric myeloid sarcoma 1 ½ years after allogeneic stem cell transplant., Case Presentation: Sixty-nine-year-old male who was diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in 2006 and transitional cell bladder carcinoma in 2008. In 2011, he developed therapy-related myeloid neoplasm t(7;22) and no excess blasts. He was treated with Vidaza followed by a MUD hematopoietic stem cell transplant on 8/24/2012. In 2013 the patient developed anorexia and gastric biopsies showed severe gastritis. Repeat gastric biopsy on 02/05/2014 showed an extensive mononuclear infiltrate which could easily be confused with lymphocytes but staining showed myeloid sarcoma. Marrow was negative. The patient remained refractory to therapy and expired 08/10/2016., Conclusion: In summary, we report the first case of GI relapse of MDS as a myeloid sarcoma post-transplant. We seek to alert our audience of this potentially serious diagnostic pitfall, particularly one that can be relatively easily resolved on the basis of immunohistochemical profiling., Competing Interests: The Authors have no relevant conflict of interest to disclose., (© 2021 Published by Elsevier Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
11. Genomic characteristics and prognostic significance of co-mutated ASXL1/SRSF2 acute myeloid leukemia.
- Author
-
Richardson DR, Swoboda DM, Moore DT, Johnson SM, Chan O, Galeotti J, Esparza S, Hussaini MO, Van Deventer H, Foster MC, Coombs CC, Montgomery ND, Sallman DA, and Zeidner JF
- Subjects
- Adult, Aged, Aged, 80 and over, Alleles, Cell Transformation, Neoplastic genetics, Cocarcinogenesis genetics, Female, High-Throughput Nucleotide Sequencing, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute classification, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Prognosis, Repressor Proteins physiology, Retrospective Studies, Serine-Arginine Splicing Factors physiology, Leukemia, Myeloid, Acute genetics, Mutation, Repressor Proteins genetics, Serine-Arginine Splicing Factors genetics
- Abstract
The ASXL1 and SRSF2 mutations in AML are frequently found in patients with preexisting myeloid malignancies and are individually associated with poor outcomes. In this multi-institutional retrospective analysis, we assessed the genetic features and clinical outcomes of 43 patients with ASXL1
mut SRSF2mut AML and compared outcomes to patients with either ASXL1 (n = 57) or SRSF2 (n = 70) mutations. Twenty-six (60%) had secondary-AML (s-AML). Variant allele fractions suggested that SRSF2 mutations preceded ASXL1 mutational events. Median overall survival (OS) was 7.0 months (95% CI:3.8,15.3) and was significantly longer in patients with de novo vs s-AML (15.3 vs 6.4 months, respectively; P = .04 on adjusted analysis). Compared to ASXL1mut SRSF2wt and ASXL1wt SRSF2mut , co-mutated patients had a 1.4 and 1.6 times increase in the probability of death, respectively (P = .049), with a trend towards inferior OS (median OS = 7.0 vs 11.5 vs 10.9 months, respectively; P = .10). Multivariable analysis suggests this difference in OS is attributable to the high proportion of s-AML patients in the co-mutated cohort (60% vs 32% and 23%, respectively). Although this study is limited by the retrospective data collection and the relatively small sample size, these data suggest that ASXL1mut SRSF2mut AML is a distinct subgroup of AML frequently associated with s-AML and differs from ASXL1mut SRSF2wt /ASXL1wt SRSF2mut with respect to etiology and leukemogenesis., (© 2021 Wiley Periodicals LLC.)- Published
- 2021
- Full Text
- View/download PDF
12. Interrogation of molecular profiles can help in differentiating between MDS and AML with MDS-related changes.
- Author
-
Badar T, Szabo A, Sallman D, Komrojki R, Lancet J, Padron E, Song J, and Hussaini MO
- Subjects
- Humans, Mutation, Nucleophosmin, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute genetics, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes genetics
- Abstract
A subset of AML with myelodysplastic syndrome (MDS)-related changes (MRCs) occurs without a documented MDS phase. We studied genomic profile of 646 patients: 310 with MDS, 167 with AML without (w/o) MRC, 99 with primary (p) AML-MRC, and 70 with secondary (s) AML-MRC and sought to find differences in mutational patterns. Among the 32-myeloid associated genes studied, SF3B1 ( p ≤ .001) was significantly mutated in higher proportion of patients with MDS, compared to other categories. NPM1 ( p < .001), FLT3 ITD ( p = .08), and NRAS ( p = .02) mutations showed trend toward significance for AML w/o MRC, compared to other categories. In pAML-MRC, TP53 ( p < .001) was significantly mutated in higher proportion of patients. Similarly, SETBP1 ( p = .001), RUNX1 ( p = .004), and SRSF2 ( p = .04) mutations were more commonly seen in sAML-MRC. While these signatures may not be diagnostically discriminatory, they may help in disease categorization when other data are absent or in challenging cases.
- Published
- 2020
- Full Text
- View/download PDF
13. Concurrent mutations in other epigenetic modulators portend better prognosis in BCOR-mutated myelodysplastic syndrome.
- Author
-
Badaat I, Mirza S, Padron E, Sallman D, Komrokji R, Song J, and Hussaini MO
- Subjects
- Aged, DNA Methylation, Female, Humans, Male, Prognosis, Biomarkers, Tumor metabolism, Epigenesis, Genetic genetics, Mutation genetics, Myelodysplastic Syndromes genetics, Neoplasm Proteins genetics, Proto-Oncogene Proteins metabolism, Repressor Proteins metabolism
- Abstract
Introduction: The role of single mutations has been extensively studied myelodysplastic syndromes (MDS), but the impact of genetic aberrations in the context of other mutations is less well understood. BCOR is an epigenetic transcriptional corepressor. In MDS, BCOR mutations are rare and certain mutations are associated with poor prognosis. Our aim was to investigate the role of concurrent mutations in epigenetic MDS-driver genes in BCOR -mutated MDS. We hypothesised that these would be redundant and would not contribute to worse prognosis., Methods: Internal Next Generation Sequencing (NGS) database with targeted genetic profiling of >4000 tumor cases was queried to locate cases of MDS with BCL6 Corepressor protein ( BCOR ) mutations only (pBCOR) and cBCOR (comutated epigenetic modulators: TET2 , ASXL1 , DNMT3A , EZH2 , IDH2 , IDH1 , BCORL1 , ATRX ). Overall survival was determined by chart review. Fischer's exact test and unpaired t-test was performed for statistical analysis., Results: 25 patients with cBCOR were detected. Only five MDS patients with pBCOR were found. The number of patients with comutations (cBCOR) in epigenetic modulators comprised TET2 (n=5), ASXL1 (n=9), DNMT3A (n=11), EZH2 (n=2), IDH2 (n=4), IDH1 (n=1), BCORL1 (n=3), ATRX (n=1). cBCOR overall survival was 23.8 months versus 11.8 months for pBCOR group., Conclusions: In this study, we confirm the rarity of BCOR mutations. Our results show that there is a trend towards poorer prognosis in patient with pBCOR versus cBCOR although statistical significance was not reached. This may be due to enrichment of poor cytogenetics in pBCOR or increased responsiveness to hypomethylating agents in cBCOR. Larger studies are needed to validate our data., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
- Full Text
- View/download PDF
14. Detection of Novel t(12;17)(p12;p13) in Relapsed Refractory Acute Myeloid Leukemia by Anchored Multiplex PCR(AMP)-based Next-Generation Sequencing.
- Author
-
Badar T, Johnson L, Trifilo K, Wang H, Kudlow BA, Padron E, Pappenhausen PR, and Hussaini MO
- Subjects
- Frameshift Mutation, Humans, Kruppel-Like Transcription Factors genetics, Kruppel-Like Transcription Factors metabolism, Male, Middle Aged, Oncogene Proteins, Fusion genetics, Oncogene Proteins, Fusion metabolism, Proto-Oncogene Proteins c-ets genetics, Proto-Oncogene Proteins c-ets metabolism, Recurrence, Repressor Proteins genetics, Repressor Proteins metabolism, ETS Translocation Variant 6 Protein, Chromosomes, Human, Pair 12 genetics, Chromosomes, Human, Pair 17 genetics, High-Throughput Nucleotide Sequencing, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute metabolism, Leukemia, Myeloid, Acute pathology, Polymerase Chain Reaction, Translocation, Genetic
- Abstract
Although several technologies can be used to detect gene fusions, anchored multiplex PCR next-generation sequencing (AMP-NGS) offers the advantage of novel fusion detection and the ability to multiplex multitudinous genes. We applied AMP-NGS technology in the evaluation of a 56-year-old gentleman with myelodysplastic syndrome transformed acute myeloid leukemia (AML). Patient was initially diagnosed with low-risk myelodysplastic syndrome-refractory cytopenias and multilineage dysplasia (MDS-RCMD), progressed to AML after failing hypomethylating agent therapy. At progression patients had normal cytogenetics but NGS profiling showed ETV6 c.416_417del CT frame shift and U2AF1 S34F mutations. Patient attains brief remission of 2 months after induction chemotherapy and then he was refractory to 2 salvage chemotherapy regimens. Reassessment after failing second salvage, identified t(12;17)(p13;p13)[20] by karyotype. It was postulated that the 12p13 locus might represent a new rearrangement of ETV6. AMP-NGS confirmed involvement of the ETV6 with discovery of a novel fusion partner, HIC1. The detection of the novel fusion partners was supported by the breakpoints originally observed by karyotype. This discovery of ETV6-HIC1 gene fusion by AMP-NGS technology provided new insight into a leukemogenic pathway in AML. Future use of this technology can serve as an adjunct tool in workup of patients with AML and can also help in formulating therapeutic strategies.
- Published
- 2019
- Full Text
- View/download PDF
15. Principles for the Oncologist in Caring for Muslim Patients.
- Author
-
Farooqi B, Modi A, Hussaini MO, Markham MJ, and Duff JM
- Subjects
- Diet, Fasting, Humans, Interpersonal Relations, Oncologists, Patient Care, Islam, Neoplasms therapy, Religion and Medicine
- Published
- 2018
- Full Text
- View/download PDF
16. Genetic Landscape of Acute Myeloid Leukemia Interrogated by Next-generation Sequencing: A Large Cancer Center Experience.
- Author
-
Hussaini MO, Mirza AS, Komrokji R, Lancet J, Padron E, and Song J
- Subjects
- Female, High-Throughput Nucleotide Sequencing methods, Humans, Leukemia, Myeloid, Acute pathology, Male, Leukemia, Myeloid, Acute genetics
- Abstract
Background/aim: Acute myeloid leukemia (AML) represents a heterogeneous disease with varying morphologic, immunophenotypic, and genetic features, along with varying patient outcomes. The genomic tractability of AML makes it amenable for targeted next-generation sequencing (NGS) testing clinically., Materials and Methods: One hundred eights-seven unique patients with a diagnosis of acute myeloid leukemia between May 2011 and Oct 2014 and with mutational analysis by NGS were included in this study. The distribution of gene mutations was investigated in different subcategories of AML., Results: Most patients in this study (n=182) received Genoptix testing (either 5-gene panel or 21-gene panel). In 130/187 (70%) cases, there was an average of 2.3 mutations per case (range=0-7 mutations). We specifically mention mutations in 32 genes, their significance and co-occurrence as detected in different types of AML., Conclusion: The genetic heterogeneity of AML signifies the importance of taking a personalized-medicine approach to the management of patients with AML., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
17. Transformation of T-Cell Acute Lymphoblastic Lymphoma to Peripheral T-Cell Lymphoma: A Report of Two Cases.
- Author
-
Markow M, Mirza AS, Perez L, Shao H, Horna P, Anasetti C, Sokol L, and Hussaini MO
- Abstract
Nonhepatosplenic/noncutaneous γδ peripheral T-cell lymphoma (NHNC γδ PTCL) represents a miscellaneous group of unrelated T-cell lymphomas of which only isolated cases have been reported. We describe two cases of transformation from T-lymphoblastic leukemia/lymphoma to NHNC γδ PTCL. Transformation into more aggressive disease is a rare event in T-cell lineage-derived hematologic malignancies compared to B-cell neoplasms. Nevertheless, both of our cases involved relapse as PTCL manifested with skin involvement and an overt shift from blastic morphology to large granular leukemia-like mature T cells. Among other notable molecular characteristics, expression of immature markers such as TdT was lost in both cases. Based on cytogenetics, phenotype, and morphology, both patients represent a novel phenomenon of clonal transformation from T-ALL to PTCL which has rarely been reported in the literature. Such transformation may carry important diagnostic and biological implications.
- Published
- 2018
- Full Text
- View/download PDF
18. Somatic Sequencing Identifies Trametinib-Responsive Myelodysplastic Syndrome and Finds Acquired Clonal Hematopoiesis of Indeterminate Potential.
- Author
-
Vela CM, Van den Bergh M, Gillis NK, Ball M, Hussaini MO, Walko CM, Hicks JK, Perez L, Padron E, and Komrokji RS
- Abstract
Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Cory M. VelaNo relationship to discloseMagali Van den BerghNo relationship to discloseNancy K. GillisNo relationship to discloseMarkus BallNo relationship to discloseMohammad O. HussainiNo relationship to discloseChristine M. WalkoHonoraria: Merck, Bristol-Myers SquibbJ. Kevin HicksNo relationship to discloseLia PerezNo relationship to discloseEric PadronHonoraria: Incyte, Cell Therapeutics, Cell Therapeutics (Inst) Research Funding: Incyte (Inst)Rami S. KomrokjiStock and Other Ownership Interests: Abbvie Consulting or Advisory Role: Celgene, Novartis Speakers' Bureau: Novartis, Alexion Pharmaceuticals Research Funding: Incyte (Inst), Celgene (Inst), GlaxoSmithKline (Inst), Eleos (Inst), Boehringer Ingelheim (Inst) Travel, Accommodations, Expenses: Celgene, Incyte, Alexion Pharmaceuticals, Novartis
- Published
- 2018
- Full Text
- View/download PDF
19. Sentinel case of Richter transformation from chronic lymphocytic leukaemia/small lymphocytic lymphoma to CD3+ diffuse large B-cell lymphoma.
- Author
-
Ismail A, Mallick JA, Qin D, and Hussaini MO
- Subjects
- Aged, 80 and over, Cell Transformation, Neoplastic pathology, Flow Cytometry, Humans, Lymphatic Metastasis, Male, Head and Neck Neoplasms pathology, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
Aim: To report the first case of a Richter syndrome where small lymphocytic lymphoma (SLL) progressed to a CD3+ diffuse large B-cell lymphoma (DLBCL)., Methods: Macrodissection of small and large cell lymphomatous components was performed. This was followed by flow cytometric analysis along with molecular B-cell immunoglobulin (heavy and light chains) and T-cell receptor (γ and β chains) gene rearrangement studies to investigate a clonal relationship between the components., Results: The immunophenotypic profile was similar between small and large cell components of the lymphoma by flow cytometry. Furthermore, shared clonal peaks were observed between both components based on molecular B-cell and T-cell receptor gene rearrangement studies, confirming a clonal relationship., Conclusions: Chronic lymphocytic leukaemia/SLL may rarely undergo Richter transformation to a DLBCL demonstrating lineage infidelity. This is a potentially important diagnostic pitfall and such cases should not be confused with a de novo T-cell lymphoma., Competing Interests: Competing interests: None., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
- Published
- 2017
- Full Text
- View/download PDF
20. EBV-positive Richter's syndrome with laboratory features of Burkitt's lymphoma, in Ibrutinib-treated chronic lymphocytic leukemia.
- Author
-
Hussaini MO, Rehman A, Chavez JC, Pinilla-Ibarz J, and Horna P
- Subjects
- Adenine analogs & derivatives, Antineoplastic Agents therapeutic use, Bone Marrow pathology, Diagnosis, Differential, Disease Progression, Epstein-Barr Virus Infections virology, Humans, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Male, Middle Aged, Oncogene Proteins, Fusion genetics, Piperidines, Protein Kinase Inhibitors therapeutic use, Pyrazoles therapeutic use, Pyrimidines therapeutic use, Burkitt Lymphoma diagnosis, Epstein-Barr Virus Infections complications, Herpesvirus 4, Human, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse etiology
- Published
- 2017
- Full Text
- View/download PDF
21. CD4-positive diffuse large B-cell lymphoma: A variant with aggressive clinical potential.
- Author
-
Hussaini MO, Kreisel FH, Hassan A, Nguyen TT, and Frater JL
- Abstract
CD4 expression is rare in diffuse large B-cell lymphoma (DLBCL), with 4 previously reported cases. Its significance is uncertain. We report five patients with CD4(+) DLBCL and one CD4(+) primary mediastinal large B-cell lymphoma. Cases were identified by searching the electronic database of the department; each was reviewed. Average age was 56 years. Neoplastic cells expressed CD20 (5/6 tested cases). BCL2/BCL6 expression were seen in 3/3 tested cases, suggesting a germinal center origin. Additionally, expression of T-cell antigens CD2 and CD5 was noted in 2/2 and CD7 in 1/1 tested case. CD3 was negative in all. Lymph nodes were commonly involved (67%). Patients received chemotherapy +/- radiation (6/6) and bone marrow transplant (2/6). Average survival was 44.2 mo. CD4 expression in DLBCL raises questions of lineage commitment. CD4(+) DLBCL is rare; care should be exercised not to diagnose these as T-cell lymphomas. A subset behaves aggressively., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest.
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.