Weina Chen

University of Texas Southwestern Medical Center, Dallas, Texas, United States

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Publications (46)144.01 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Blastic plasmacytoid dendritic cell neoplasm is an exceedingly rare hematologic malignancy derived from the precursors of plasmacytoid dendritic cells. Mutations in isocitrate dehydrogenase (IDH) 1 and 2 genes have been discovered in a range of neoplasms including glioma, acute myeloid leukemia, chondrosarcoma, and intrahepatic cholangiocarcinoma. Mutant IDH acquires neomorphic enzymatic activity to generate the oncometabolite d-2-hydroxyglutarate (d-2HG). Here, we describe the first case of an IDH2 R140Q-mutated blastic plasmacytoid dendritic cell neoplasm in a patient with markedly elevated plasma d-2HG. This finding expands the spectrum of neoplasms with increased d-2HG in association with IDH mutation. The roles of IDH mutation and d-2HG in disease pathogenesis and assessment of clinical response are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.
    Human pathology 11/2014; · 3.03 Impact Factor
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    ABSTRACT: Background: Acute megakaryoblastic leukemia (AMKL) is a rare form of acute myeloid leukemia that encompasses three distinct subgroups, children with Down syndrome (DS-AMKL), children without DS (non-DS-AMKL) and adults (adult-AMKL). We hypothesize that the biological differences in the subtypes of AMKL may be reflected in distinct immunophenotypic (IP) features. Our aims were to employ mutiparameter flow cytometry to establish a comprehensive IP spectrum of AMKL in multiple demographic groups and to determine whether the subtypes of AMKL demonstrate distinct immunophenotypes. Methods: Thirty-seven AMKL cases were retrieved and subdivided into these three groups. Multiparameter flow cytometry was used to determine and compare the immunophenotypes. Available clinical, cytogenetic, and morphologic data were reviewed to confirm diagnoses. Results: While there is commonality in the expression pattern for a wide range of myelomonocytic markers in these three subtypes of AMKL, blasts in DS-AMKL were more likely to express CD7 and CD11b than those in non-DS-AMKL and adult-AMKL. Furthermore, blasts in DS-AMKL were more likely to express CD13, CD33 and CD36 than non-DS pediatric AMKL, and showed greater CD56 expression compared to adult AMKL. Conclusions: These results indicate that DS-AMKL is related to but immunophenotypically distinct from non-DS-AMKL and adult-AMKL. This distinct immunophenotypic pattern, co-expression of CD7 and CD11b, has practical implications for characterization of AMKL. © 2014 Clinical Cytometry Society.
    Cytometry Part B Clinical Cytometry 10/2014; · 2.23 Impact Factor
  • Franklin Fuda, Weina Chen
    Cytometry Part B Clinical Cytometry 01/2014; · 2.23 Impact Factor
  • Franklin Fuda, Weina Chen
    Cytometry Part B Clinical Cytometry 01/2014; · 2.23 Impact Factor
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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes according to their gene-expression signatures. In this study, we assessed a cohort of 893 de novo DLBCL patients treated with R-CHOP therapy. We show that MYC/BCL2 protein co-expression occurred significantly more commonly in the ABC subtype. The ABC and GCB subtypes had similar prognoses in DLBCL with MYC/BCL2 co-expression as well as in DLBCL without MYC/BCL2 co-expression. Consistent with the notion that the prognostic difference between the two subtypes was attributable to MYC/BCL2 co-expression, the difference in gene-expression signatures between the two subtypes was dramatically diminished in the absence of MYC/BCL2 co-expression. Furthermore, DLBCL with MYC/BCL2 co-expression demonstrated a signature of marked downregulation of genes encoding extracellular matrix proteins, those involving matrix deposition/remodeling and cell adhesion, and upregulation of proliferation-associated genes. We conclude that MYC/BCL2 co-expression in DLBCL is associated with an aggressive clinical course, is more common in the ABC subtype, and contributes to the overall inferior prognosis of patients with ABC-DLBCL. Furthermore, the data suggest that MYC/BCL2 co-expression, rather than cell of origin classification, is a better predictor of prognosis in patients with DLBCL treated with R-CHOP therapy.
    Blood 02/2013; · 9.78 Impact Factor
  • Weina Chen
    Cytometry Part B Clinical Cytometry 01/2013; · 2.23 Impact Factor
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    ABSTRACT: Approximately 20% of unselected cases and 30% cytogenetically diploid cases of acute myeloid leukemia (AML) and 80% of grade II-III gliomas and secondary glioblastomas carry mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes. IDH1/2 mutations prevent oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) and modulate the function of IDH (neomorphic activity) thereby facilitating reduction of α-KG to D-2-hydroxyglutarate (D-2HG), a putative oncometabolite. D-2HG is thought to act as a competitive inhibitor of α-KG-dependent dioxygenases that include prolyl hydroxylases and chromatin-modifying enzymes. The end result is a global increase of cellular DNA hypermethylation and alterations of the cellular epigenetic state, which has been proposed to play a role in the development of a variety of tumors. In this review, we provide an update on potential molecular mechanisms linking IDH1/2 mutations and the resulting oncometabolite, D-2HG, with malignant transformation. In addition, in patients with AML and glioma we focus on the associations between IDH1/2 mutations and clinical, morphologic, cytogenetic, and molecular characteristics.
    Frontiers in Oncology 01/2013; 3:169.
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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin Lymphoma comprising of greater than 30% of adult non-Hodgkin Lymphomas. DLBCL represents a diverse set of lymphomas, defined as diffuse proliferation of large B lymphoid cells. Numerous cytogenetic studies including karyotypes and fluorescent in situ hybridization (FISH), as well as morphological, biological, clinical, microarray and sequencing technologies have attempted to categorize DLBCL into morphological variants, molecular and immunophenotypic subgroups, as well as distinct disease entities. Despite such efforts, most lymphoma remains undistinguishable and falls into DLBCL, not otherwise specified (DLBCL-NOS). The advent of microarray-based studies (chromosome, RNA, gene expression, etc) has provided a plethora of high-resolution data that could potentially facilitate the finer classification of DLBCL. This review covers the microarray data currently published for DLBCL. We will focus on these types of data; 1) array based CGH; 2) classical CGH; and 3) gene expression profiling studies. The aims of this review were three-fold: (1) to catalog chromosome loci that are present in at least 20% or more of distinct DLBCL subtypes; a detailed list of gains and losses for different subtypes was generated in a table form to illustrate specific chromosome loci affected in selected subtypes; (2) to determine common and distinct copy number alterations among the different subtypes and based on this information, characteristic and similar chromosome loci for the different subtypes were depicted in two separate chromosome ideograms; and, (3) to list re-classified subtypes and those that remained indistinguishable after review of the microarray data. To the best of our knowledge, this is the first effort to compile and review available literatures on microarray analysis data and their practical utility in classifying DLBCL subtypes.Although conventional cytogenetic methods such as Karyotypes and FISH have played a major role in classification schemes of lymphomas, better classification models are clearly needed to further understanding the biology, disease outcome and therapeutic management of DLBCL. In summary, microarray data reviewed here can provide better subtype specific classifications models for DLBCL.
    Journal of Hematology & Oncology 09/2012; 5:54. · 4.46 Impact Factor
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    ABSTRACT: Acute myeloid leukemia is a heterogeneous group of diseases. Mutations of the isocitrate dehydrogenase (IDH) genes represent a novel class of point mutations in acute myeloid leukemia. These mutations prevent oxidative decarboxylation of isocitrate to α-ketoglutarate and confer novel enzymatic activity, facilitating the reduction of α-ketoglutarate to d-2-hydroxyglutarate, a putative oncometabolite. IDH1/IDH2 mutations are heterozygous, and their combined frequency is approximately 17% in unselected acute myeloid leukemia cases, 27% in cytogenetically normal acute myeloid leukemia cases, and up to 67% in acute myeloid leukemia cases with cuplike nuclei. These mutations are largely mutually exclusive. Despite many similarities of IDH1 and IDH2 mutations, it is possible that they represent distinct molecular or clinical subgroups of acute myeloid leukemia. All known mutations involve arginine (R), in codon 132 of IDH1 or codon 140 or 172 of IDH2. IDH1(R132) and IDH2(R140) mutations are frequently accompanied by normal cytogenetics and NPM1 mutation, whereas IDH2(R172) is frequently the only mutation detected in acute myeloid leukemia. There is increasing evidence that the prognostic impact of IDH1/2 mutations varies according to the specific mutation and also depends on the context of concurrent mutations of other genes. IDH1(R132) mutation may predict poor outcome in a subset of patients with molecular low-risk acute myeloid leukemia, whereas IDH2(R172) mutations confer a poor prognosis in patients with acute myeloid leukemia. Expression of IDH1/2 mutants induces an increase in global DNA hypermethylation and inhibits TET2-induced cytosine 5-hydroxymethylation, DNA demethylation. These data suggest that IDH1/2 mutations constitute a distinct mutational class in acute myeloid leukemia, which affects the epigenetic state, an important consideration for the development of therapeutic agents.
    Human pathology 08/2012; 43(10):1541-51. · 3.03 Impact Factor
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    ABSTRACT: Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell lymphoma strongly associated with human immunodeficiency virus (HIV) infection. The authors conducted a multi-institutional, retrospective study to describe characteristics and determine prognostic factors in HIV-associated PBL. For this study, the investigators included consecutive, HIV-positive patients diagnosed between the years 2000 and 2010 whose tumors had a plasmablastic morphology, were cluster of differentiation 20 (CD20)-negative, and expressed markers of plasmacytic differentiation. Fifty patients from 13 institutions were evaluated. The median age was 43 years, and there was a male predominance. The median count of cells that were positive for CD4 (a glycoprotein expressed on the surface of T-helper cells, monocytes, macrophages, and dendritic cells) was 206 cells/mm(3) . At presentation, 90% of patients had extranodal involvement, 69% presented with advanced stage disease, and 27% had oral involvement. Rearrangements of v-myc myelocytomatosis viral oncogene homolog (MYC) were detected in 41% of the tested patients. Eighty-five percent of patients received chemotherapy, with 63% receiving cyclophosphamide, doxorubicin, vincristine, and prednisone and 37% receiving more intensive regimens. The complete response (CR) rate was 66%. The median overall survival (OS) was 11 months regardless of the intensity of chemotherapy. In the survival analysis, an Eastern Cooperative Oncology Group performance status ≥2, advanced stage, and MYC rearrangements were associated significantly with a worse outcome, whereas attaining a CR with chemotherapy was associated with a better outcome. The prognosis of PBL in HIV-infected individuals remains poor in the highly active antiretroviral therapy era. Intensive chemotherapy regimens do not seem to increase survival in patients with HIV-associated PBL. Cancer 2012. © 2012 American Cancer Society.
    Cancer 04/2012; 118(21):5270-7. · 5.20 Impact Factor
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    ABSTRACT: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a B-cell neoplasm that is typically CD5 negative. We describe the clinicopathologic, immunophenotypic, and cytogenetic features of 14 cases of CD5+ MALT lymphoma. There were 9 men and 5 women (median age, 68 years; range, 34-87 years). MALT lymphoma was initially diagnosed in salivary glands (n = 4), nasopharynx (n = 2), and 1 case each in conjunctiva, thyroid, stomach, colon, skin, lung, kidney, and retroperitoneum. Two patients had localized disease; 9 had disseminated disease with generalized lymphadenopathy (n = 8), multifocal lymphoma (n = 6), or bone marrow involvement (n = 5). No staging information was available for the remaining patients. None presented with B symptoms, splenomegaly, cytopenias, lymphocytosis, monoclonal gammopathy, or elevated serum lactate dehyrogenase. Serum β2-microglobulin was elevated in 6. Morphologically, the neoplasms had features typical of MALT lymphoma being composed of small- to medium-sized cells with round to slightly irregular nuclear contours and moderate amount of cytoplasm. Lymphoepithelial lesions were noted in 4 cases. CD5 was positive in all cases by immunohistochemistry (n = 12) and/or flow cytometry (n = 11). All cases assessed were negative for cyclin D1 (13/13) and CD10 (11/11). Conventional cytogenetics in 7 cases showed trisomy 3 in 3 and diploid in 4. With a median follow-up of 71 months (range, 2-131 months), overall survival at 5 years was 100%, although 5 patients required chemotherapy. Our results show that CD5 expression is rare in MALT lymphoma, and is often associated with nongastric disease and an increased tendency to present with disseminated disease. Overall survival is excellent with appropriate therapy.
    Human pathology 03/2012; 43(9):1436-43. · 3.03 Impact Factor
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    ABSTRACT: In chronic myelogenous leukemia, chromosomal abnormalities in Philadelphia-negative cells are rare and usually transient, but can infrequently lead to myelodysplastic syndrome and/or acute myeloid leukemia. We report an 82-ear-old patient with an 11-year history of chronic myelogenous leukemia, in complete cytogenetic response, who developed Philadelphia-negative t(15;17)/PMLRARA acute promyelocytic leukemia. This isolated case reaffirms several important clinicopathologic and biologic aspects of chronic myelogenous leukemia, and sheds a unique light on its Philadelphia-negative hematopoiesis. It also underlines the importance of continued cytogenetic monitoring of patients in complete cytogenetic response for the emergence of new chromosomal abnormalities.
    Cancer Genetics 03/2012; 205(3):124-7. · 1.92 Impact Factor
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    ABSTRACT: FMS-like tyrosine kinase 3 (FLT3) mutation in T lymphoblastic leukemia/lymphoma (T-LL) is rare (∼4%) and reported only in cases with CD117 expression. This study aimed to identify the immunophenotypic features that may predict FLT3 mutations. We report 3 (43%) of 7 CD117(+) T-LL cases harboring FLT3-internal tandem duplication mutation. Compared with 4 FLT3-unmutated cases, all 3 FLT3-mutated cases had a distinct immunophenotype (CD1a(-)/CD2(+)/CD7(+)/CD34(+)/CD117(uniform+)/Tdt(+)) corresponding to the stage of earliest thymic T-cell progenitors possessing myeloid lineage potential. Indeed, all FLT3-mutated T-LL cases expressed myeloperoxidase on a very small subset of blasts and, thus, may be further considered a mixed phenotype acute leukemia, T/myeloid, by the 2008 World Health Organization classification scheme. We conclude that this unique immunophenotype (CD1a(-)/CD2(+)/CD7(+)/CD34(+)/CD117(+)/Tdt(+)) is a better predictor of FLT3 mutation than sole CD117 expression.
    Annals of diagnostic pathology 11/2011; 16(1):16-20.
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    ABSTRACT: Although the loss of B-lineage-specific gene expression is a distinctive feature of plasmablastic lymphoma, the underlying mechanism remains poorly understood. A candidate for this mechanism is Notch1 signaling, which interferes with the activity of B-cell-specific transcription factors E2A and early B-cell factor and positively regulates the mammalian target of rapamycin (mTOR) pathway. To explore the mechanism of loss of B-cell phenotype by correlating expression of B-cell markers with that of Notch1 and downstream targets of the mTOR pathway in plasmablastic lymphoma. A combination of flow cytometric and immunohistochemical immunophenotyping techniques was used on 9 cases of plasmablastic lymphoma to correlate loss of B-cell markers with expression of Notch1 and downstream activation of the mTOR pathway. These results are compared with 5 cases of primary effusion lymphoma and 21 cases of plasma cell myeloma. Plasmablastic lymphoma cases exhibit nearly complete loss of B-cell-associated markers and uniform expression of Notch1, with a predominantly nuclear staining pattern. There is a concurrent activation of the mTOR pathway, indicated by expression of mTOR targets eukaryotic initiation factor 4E-binding protein 1 and phosphorylated ribosomal protein S6 in most cases. Similar results are seen in cases of primary effusion lymphoma and plasma cell myeloma. These findings suggest that activation of Notch1 may be involved in suppression of B-cell-specific gene expression and global loss of the B-cell phenotype in plasmablastic lymphoma, similar to primary effusion lymphoma and plasma cell myeloma. Thus, there might be a role for the Notch1 and mTOR pathways in the pathogenesis and therapy of plasmablastic lymphoma.
    Archives of pathology & laboratory medicine 06/2011; 135(6):770-5. · 2.78 Impact Factor
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    Leukemia research 05/2011; 35(9):e151-3. · 2.36 Impact Factor
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    British Journal of Haematology 04/2011; 155(1):125-8. · 4.94 Impact Factor
  • Journal of the Association of Genetic Technologists 01/2011; 37(4):213-5.
  • British Journal of Haematology 01/2011; 155(1). · 4.94 Impact Factor
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    ABSTRACT: Rearrangements of JAK2 are rare and have been described in various hematological neoplasms. We report a novel JAK2 rearrangement resulting from a t(9;22)(p24;q11.2) in a 14-year-old male with a diagnosis of B lymphoblastic leukemia. He was treated with Children's Oncology Group's protocol (AALL0232) but failed to achieve remission by day 29. He underwent a second induction and entered remission. His clinical course suggested that this JAK2 rearrangement might portend an unfavorable prognosis. This case brings the total number of JAK2 rearranged lymphoblastic leukemia cases in the literature to seven. The molecular genetic and clinicopathologic features of these cases were reviewed.
    Leukemia research 12/2010; 34(12):1674-6. · 2.36 Impact Factor
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    ABSTRACT: Activating mutations of the FLT3 gene mediate leukemogenesis, at least in part, through activation of PI3K/AKT. The mammalian target of rapamycin (mTOR)-Raptor signaling pathway is known to act downstream of AKT. Here we show that the mTOR effectors, 4EBP1, p70S6K and rpS6, are highly activated in cultured and primary FLT3-mutated acute myeloid leukemia (AML) cells. Introduction of FLT3-ITD expressing constitutively activated FLT3 kinase further activates mTOR and its downstream effectors in BaF3 cells. We also found that mTOR signaling contributes to tumor cell survival, as demonstrated by pharmacologic inhibition of PI3K/AKT/mTOR, or total silencing of the mTOR gene. Furthermore, inhibition of FLT3 kinase results in downregulation of mTOR signaling associated with decreased survival of FLT3-mutated AML cells. These findings suggest that mTOR signaling operates downstream of activated FLT3 kinase thus contributing to tumor cell survival, and may represent a promising therapeutic target for AML patients with mutated-FLT3.
    Molecular Cancer 11/2010; 9:292. · 5.13 Impact Factor

Publication Stats

396 Citations
144.01 Total Impact Points

Institutions

  • 2004–2014
    • University of Texas Southwestern Medical Center
      • • Department of Pathology
      • • Division of Hematology/Oncology
      Dallas, Texas, United States
  • 2012
    • Quest Diagnostics Incorporated
      Madison, New Jersey, United States
  • 2005–2010
    • University of Texas MD Anderson Cancer Center
      • Department of Hematopathology
      Houston, TX, United States