Huan-You Wang

SC35 Plays a Role in T Cell Development and Alternative Splicing of CD45

Molecular diversity via alternative splicing is important for cellular function and development. SR proteins are strong candidate regulators of alternative splicing because they can modulate splice site selection. However, endogenous substrates for SR proteins are largely unknown, and their roles as splicing regulators in vertebrate development are unclear. Here we report that Cre-mediated conditional deletion of the prototypical SR protein SC35 in the thymus causes a defect in T cell maturation. Deletion of SC35 alters alternative splicing of CD45, a receptor tyrosine phosphatase known to be regulated by differential splicing during thymocyte development and activation. This study establishes a model to address the function of SR proteins in physiological settings and reveals a critical role of SC35 in a T cell-specific regulated splicing pathway.

ROR1 is expressed on hematogones (non-neoplastic human B-lymphocyte precursors) and a minority of precursor-B acute lymphoblastic leukemia.

ROR1 is a receptor tyrosine kinase expressed during embryogenesis, on chronic lymphocytic leukemia (CLL) and in other malignancies. Hematogones (non-neoplastic B-lymphocyte precursors) express surface ROR1 at an intermediate stage of maturation that lacks CD34 or TdT. The neoplastic counterpart to hematogones is precursor-B acute lymphoblastic leukemia (B-ALL), but less than 10% of B-ALL express surface ROR1, and these ROR1+ B-ALL cases have an unusually high frequency of lacking CD34 and/or having t(1;19), a chromosomal translocation that defines a specific subtype of B-ALL.

Novel FNDC3B and MECOM fusion and WT1 L378fs* 7 frameshift mutation in an acute myeloid leukaemia patient with cytomorphological and immunophenotypic features reminiscent of acute promyelocytic leukaemia.

Author(s): Wang, Huan-You; McMahon, Caitlin; Ali, Siraj M; Young, Lauren E; Yekezare, Somaye; Ross, Jeffrey S; Ball, Edward D

t(4;22)(q12;q11.2) involving presumptive platelet-derived growth factor receptor A and break cluster region in a patient with mixed phenotype acute leukemia

The patient is a 45-year-old woman with a history of breast cancer who had been treated 1 year ago with radiation and chemotherapy. Flow cytometric analysis of bone marrow aspirate revealed 81% blasts positive for CD4, CD11c (partial), CD13, CD19 (partial), cytoplasmic CD22, CD34, CD36, CD45, cytoplasmic CD79a, CD117 (partial), HLA-DR, and terminal deoxynucleotide transferase, consistent with a mixed phenotype acute leukemia (B/myeloid lineage). Conventional karyotypic analysis revealed a t(4;22)(q12;q11.2) in 12 of 13 cells analyzed. Fluorescence in situ hybridization analysis using a dual-color, dual-fusion break cluster region/ABL probe set showed no break cluster region/ABL translocation but an extra break cluster region signal in 85% (170/200) of cells, consistent with a translocation involving the break cluster region gene at 22q11.2. A FIP1L1/CHIC2/platelet-derived growth factor receptor α deletion/fusion probe showed signal separation in 96.5% (193/200) of interphase nuclei. Reverse transcriptase-polymerase chain reaction using sense break cluster region primers and an antisense platelet-derived growth factor receptor α primer resulted in a product of approximately 590 base pairs, consistent with the presence of a break cluster region/platelet-derived growth factor receptor α fusion gene. Because of the presumptive platelet-derived growth factor receptor α translocation and its sensitivity to tyrosine-kinase inhibitor, the patient was treated with imatinib mesylate, cytarabine, and idarubicin as induction and maintenance therapy; and she has remained free of disease for 5 months since the initial diagnosis.

Myeloid neoplasm with t(3;8)(q26;q24): report of six cases and review of the literature

Abstract Balanced translocation between chromosomes 3q26 and 8q24 is a very rare event. Here we report six patients with t(3;8)(q26;q24) either as a sole or as a part of genetic abnormalities. Five of the six patients were men with ages ranging from 41 to 84 years old. One patient had a long history of granulocyte colony stimulating factor (G-CSF) treatment. Three of the patients were initially diagnosed with acute myeloid leukemia, two with myelodysplastic syndrome and one with chronic myelogenous leukemia with blast crisis. The peripheral blood in all patients showed severe to moderate anemia; one had absolute neutropenia, one with neutrophilia; four had thrombocytopenia, two with thrombocytosis. The bone marrows from all patients showed dysmegakaryopoiesis with additional erythroid (three patients) and granulocytic (two patients) dysplasia. Cytogenetics revealed t(3;8)(q26;q24) as the sole abnormality in three patients. The majority of patients (4/6) had a poor clinical course, with an average survival of 10 months.

A rare and unique case of aggressive IgE-λ plasma cell myeloma in a 28-year-old woman presented initially as an orbital mass

A 28-year-old African-American woman presented with new onset of left exophthalmos and diplopia. Computed tomography of the head showed a solitary mass in the left orbit. Excisional biopsy revealed a diffuse infiltrate composed of exclusively λ-restricted monotypic plasma cells based on morphology and immunohistochemistry, consistent with a plasma cell neoplasia. A subsequent staging bone marrow biopsy showed involvement of the bone marrow by λ-restricted monotypic plasma cells, consistent with a plasma cell myeloma. Serum protein electrophoresis and immunofixation studies on the peripheral blood showed a monoclonal band of IgE-λ; thus, an IgE-λ plasma cell myeloma was established. Additional clinical and radiologic workups showed multiple lytic bone lesions, diffuse lymphadenopathy, a pelvic mass, multiple mesenteric soft tissue nodules, and multiple pulmonary nodules, although none of the aforementioned sites was biopsied. The patient was treated with a combination of multiple chemotherapeutic agents and localized radiation due to the aggressive nature of the disease. To the best of our knowledge, this is the first case of an IgE plasma cell myeloma in a patient under the age of 30 years old presenting as a mass in an extramedullary site.

Diagnostic pitfall: primary effusion lymphoma with rare cytokeratin immunoreactivity

![Figure][1] A 52-year-old man with history of AIDS, rectal Kaposi sarcoma, and multicentric Castleman disease was found to have diffuse lymphadenopathy, bilateral pleural effusions, and ascites. Cytology smears of the pleural effusion (panel A; Diff-Quik) showed numerous large atypical

Successful treatment of both double minute of C-MYC and BCL-2 rearrangement containing large B-cell lymphoma with subsequent unfortunate development of therapy-related acute myeloid leukemia with t(3;3)(q26.2;q21)

Double minute chromosomes (DMs), although relatively frequently encountered in solid tumors, are rare in hematologic neoplasms such as acute myeloid leukemia (AML), and even rarer in lymphoid neoplasms. t(3;3)(q26.2;q21) is a very rare genetic alteration observed in myeloid neoplasm. Herein we report an interesting and unique case of concomitant C-MYC DMs and t(14;18)-containing large B-cell lymphoma, which was successfully treated with R-hyper-CVAD; unfortunately, the patient has developed a therapy-related AML (t-AML) 2 years since the start of his lymphoma treatment. His t-AML contains both t(3;3)(q26.2;q21) and monosomy 7, and the patient died of AML 10 months after the initial diagnosis of t-AML despite clinical remission. To the best of our knowledge, this is the first reported case of C-MYC DM-containing de novo large B-cell lymphoma, which was successfully treated with complete remission, but unfortunately died of t-AML harboring t(3;3)(q21;q26).

Two cases of mantle cell lymphoma mimicking marginal zone lymphoma

Mantle cell lymphoma (MCL) is a B cell lymphoma with four morphologic variants recognized by the current World Health Organization classification. MCL mimicking marginal zone lymphoma (MZL) (MCL mimicking MZL) is the rarest variant and could be a potential diagnostic pitfall due to its deceiving “monocytoid” appearance. We report two cases of extranodal MCL mimicking MZL occurring at different sites—the oropharynx and the rectosigmoid colon. Both cases showed unexpected diffuse submucosal lymphoid infiltration of small- to medium-sized lymphocytes with focal monocytoid appearance. Immunohistochemistry showed the presence of an abnormal CD5(−)/CD10(−) B cell population expressing cyclin D1. The diagnosis of MCL was further substantiated by cytogenetic evidence of t(11;14)(q13;q32). Ki-67 proliferation indexes of both cases were low. In summary, MCL mimicking MZL may have unusual morphologic and immunophenotypic characteristics that could be a diagnostic pitfall.

JAK2 double minutes with resultant simultaneous amplification of JAK2 and CD274 in a therapy-related myelodysplastic syndrome evolving into an acute myeloid leukaemia

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