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Papers by Mohammad Jan Hussaini

Cancer Genomics - Proteomics, 2018

Leukemia & lymphoma, Jul 9, 2017

Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare entity. We present a multicenter e... more Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare entity. We present a multicenter experience of 17 patients with FISH-confirmed FGFR1 rearrangement. The clinical presentation at diagnosis included myeloproliferative neoplasm (MPN) in 4 (24%) patients, acute leukemia (AL) in 7 (41%), and concomitant MPN with AL in 6 (35%). The two most frequently observed cytogenetic abnormalities were t(8;13)(p11.2;q12)(partner gene ZMYM2) and t(8;22)(p11.2; q11.2)(BCR). Seventy-eight percent of tested patients had a RUNX1 mutation, of whom all had AL. Overall response rate to frontline therapy was 69%, and 76% of patients subsequently received allogeneic stem cell transplant (ASCT). After a median follow-up of 11 months, median progression-free survival was 15 months and median overall survival was not reached. In conclusion, FGFR1-rearranged hematologic malignancies present with features of MPN and/or AL. FGFR1 and RUNX1 are therapeutic targets for ongoing and future clinical trials.

Clinical lymphoma, myeloma & leukemia, 2018

Recent studies have shown dismal outcomes when chronic lymphocytic leukemia progresses to Richter... more Recent studies have shown dismal outcomes when chronic lymphocytic leukemia progresses to Richter syndrome after patients receive ibrutinib, with a median overall survival ranging from 2.6 to 3.5 months. Published data on efficacy of allogeneic hematopoietic cell transplantation in Richter syndrome are limited to single-center case series and registry data. We evaluated the efficacy of allogeneic transplantation in 10 patients, median age of 63 (range, 50-74) years, allografted at a median of 5 (range, 4-25) months from diagnosis of Richter syndrome. All showed an objective response to therapy before transplantation (first complete remission = 7 [70%], first partial response = 2 [20%], second partial response = 1 [10%]). Most received a myeloablative conditioning regimen (n = 7, 70%). Filgrastim-mobilized peripheral blood stem cells was the preferred cell source (n = 10, 100%). Median follow-up of surviving patients was 46 (range, 15-82) months. The 4-year overall survival was 50% (...

American Journal of Clinical Pathology, 2017

Objectives: To compare the mutational profiles of patients with primary myelofibrosis (PMF), poly... more Objectives: To compare the mutational profiles of patients with primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocytosis (ET). Methods: Next-generation sequencing results of 75 cases of PMF, 33 cases of PV, and 27 cases of ET were compared. Results: Mutation rates of ASXL1 and SRSF2 were significantly higher in PMF than in PV or ET. ASXL1 mutations appeared to be more frequently associated with risk of transformation to acute myeloid leukemia than JAK2 or TET2 mutations. The most common mutation-cytogenetic combinations in myeloproliferative neoplasm (MPN) were mutations of JAK2 or ASXL1 with del(20q) and were more common in patients with PMF and PV than in patients with ET. Differences were also found between patients with PMF and PV. Conclusions: PMF, PV, and ET show different mutational profiles, which may be helpful in resolving the differential diagnosis between MPNs. Due to the relatively small number of cases and variable testing over time, larger controlled studies are necessary to confirm the findings. Primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocytosis (ET) are common Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs), characterized by cytoses, splenomegaly, and hypercellular bone marrows with proliferation of myeloid, erythroid, and/or megakaryocytic lineages. In early stage disease, PMF usually presents with leukocytosis, PV with increased hemoglobin level, and ET with thrombocytosis. However, it is a challenge to distinguish between ET and prefibrotic/early myelofibrosis, as well as initial cases of PV from ET or even PMF. 1-3 The differential diagnosis at the intermediate stage is easier but could still be a pathologic challenge. The relevance of differentiating between these entities lies beyond an academic exercise given the different natural histories and treatment approaches for each. Survival is longest in ET (median survival of 20 Upon completion of this activity you will be able to: • discuss the application of gene mutations in the differential diagnosis of primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocytosis (ET). • discuss the significance of gene mutations in predicting prognosis of patients with PMF, PV, or ET. The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit TM per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

American Journal of Clinical Pathology, 2015

showed aberrations at the 13p11 locus. In the PTCL of patient 2, homozygous interstitial deletion... more showed aberrations at the 13p11 locus. In the PTCL of patient 2, homozygous interstitial deletion of 14q32.2 was detected, which houses BCL11B (implicated in TALL pathogenesis). Whether these PTCLs are to be considered "ALL-like," given their putative clonal derivation, or a new entity with unique biology will require analysis of more patients. We hypothesize that this novel phenomenon may be due to clonal evolution secondary to mutations in T-cell differentiation genes or a common precursor sustaining an initial transforming event followed by additional and separate transforming events in the TALL and PTCL. Herpes simplex virus (HSV) positivity in both cases raises the possibility of a viral-induced pathway.

Pathology Case Reviews, 2012

Journal of the Islamic Medical Association of North America, 1982

this study. the aUlhor has used the scientific data as a major applied tool for the better undcr:... more this study. the aUlhor has used the scientific data as a major applied tool for the better undcr:;tanding of the:: Islamic spirit. The objective examination of the Islamic Revelation in the light of the discoveries of. cience will surcly help readers appreciate the wisdom and applicability of Islam. "The mothers shall give mdl j() their uffipring for two whole years" ... Qur'an. II: 233 Islam recogn izcd the importance of infa nl nil Iril ioñ ome 1400 years ago although the uniqueness and special value of human milk has been scientifically SIGNIFICANCE OF NUTRITION: Islam, satisfying the needs and demands of all limes, witnesses the imporlance of nUlrition as reSI of all aspect ofliJe. It recommends ealing ofalllhat is good

Modern Pathology, 2011

Frozen section analysis is an essential tool for assessing margins intra-operatively to assure co... more Frozen section analysis is an essential tool for assessing margins intra-operatively to assure complete resection. Many institutions evaluate surgical defect edge tissue provided by the surgeon after the main lesion has been removed. With the increasing use of transoral laser microsurgery, this method is becoming even more prevalent. We sought to evaluate error rates at our large academic institution and to see if sampling errors could be reduced by the simple method change of taking an additional third section on these specimens. All head and neck tumor resection cases from January 2005 through August 2008 with margins evaluated by frozen section were identified by database search. These cases were analyzed by cutting two levels during frozen section and a third permanent section later. All resection cases from August 2008 through July 2009 were identified as well. These were analyzed by cutting three levels during frozen section (the third a 'much deeper' level) and a fourth permanent section later. Error rates for both of these periods were determined. Errors were separated into sampling and interpretation types. There were 4976 total frozen section specimens from 848 patients. The overall error rate was 2.4% for all frozen sections where just two levels were evaluated and was 2.5% when three levels were evaluated (P ¼ 0.67). The sampling error rate was 1.6% for two-level sectioning and 1.2% for threelevel sectioning (P ¼ 0.42). However, when considering only the frozen section cases where tumor was ultimately identified (either at the time of frozen section or on permanent sections) the sampling error rate for two-level sectioning was 15.3 versus 7.4% for three-level sectioning. This difference was statistically significant (P ¼ 0.006). Cutting a single additional 'deeper' level at the time of frozen section identifies more tumor-bearing specimens and may reduce the number of sampling errors.

Comparative Clinical Pathology, 2011

Firstly, increased Ki67 and MUM-1 staining has been associated with worse prognosis in marginal z... more Firstly, increased Ki67 and MUM-1 staining has been associated with worse prognosis in marginal zone B cell lymphomas (MZL). However, ours is the first study to assess the impact of proliferative indices on chemotherapy response. Secondly, loss of p53 and p16 tumor suppressor genes (TSG) has traditionally been associated with cancer progression. The significance of these markers in MZL was investigated. Thirdly, we explored the role of proliferative indices and tumor suppressor genes in identifying MZLs with significant plasmacytic differentiation (PD). Consecutive MZL cases (2006-2008) were identified. Slides were reviewed to confirm the diagnosis; immunohistochemical stains for Ki67, MUM-1, WT-1, p53, and p16 were subsequently performed and graded for percentage staining. Wilcoxon two-sample test and Pearson correlation coefficient were performed. Twenty-nine cases were analyzed. None of the assayed markers were correlated with treatment response. Ki67 and MUM1 expression, however, were correlated with PD (p=0.0136 and p=0.0042). A correlation between MUM1 and p16 staining was also seen (p=0.0006). IHC assay for TSGs, p53 and p16, and proliferative indices (Ki67, MUM1, WT1) is unlikely to predict treatment response in low-grade MZL. Ki67 and MUM1 staining, however, may serve as a useful adjunct in ascribing PD.

Leukemia research, 2018

T- cell prolymphocytic leukemia (T- PLL) is a rare aggressive hematological malignancy. Alemtuzum... more T- cell prolymphocytic leukemia (T- PLL) is a rare aggressive hematological malignancy. Alemtuzumab, an anti-CD52 humanized monoclonal antibody, is the treatment of choice for remission induction. Allogeneic hematopoietic cell transplantation (allo-HCT) has been described to induce durable remissions and improve survival, but data is limited. We evaluated clinical outcomes of 11 patients, median age of 56 (range, 43-71) years who underwent allo-HCT for T-PLL. The majority of cases were in the first complete remission (CR1 = 9, CR2 = 1, second partial response PR2 = 1) at time of allo-HCT. Myeloablative conditioning was the most commonly prescribed preparative regimen (n = 8, 73%) and tacrolimus plus sirolimus was most commonly prescribed regimen for graft-versus-host disease prophylaxis (n = 5, 46%). The median follow-up for surviving patients was 48 (range, 6-123) months. The 4-year progression-free survival (PFS) and overall survival (OS) were 45% (95% confidence interval (CI) = 1...