Myeloid leukemia cell differentiation protein (MCL1); B cell lymphoma 2 (BCL-2; BCL2)

Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2), regulates genes involved in cell lineage and differentiation through methylating lysine 27 on histone H3 (H3K27me3). Recurrent gain-of-function mutations of EZH2 have been identified in various cancer types, in particular, diffuse large B-cell lymphoma (DLBCL), through large-scale genome-wide association studies and EZH2 depletion or pharmacological inhibition has been shown to exert an antiproliferative effect on cancer cells, both in vitro and in vivo. In the current study, a combination of pomalidomide and GSK126 synergistically inhibited the growth of EZH2 gain-of-function mutant Diffuse large B-cell lymphoma (DLBCL) cells. Furthermore, this synergistic effect appeared to be dependent on cereblon (CRBN), a cellular receptor of pomalidomide, but not degradation of IKAROS family zinc finger 1 (IKZF1) or IKAROS family zinc finger 3 (IKZF3). RNA sequencing analyses revealed that co-treatment with GSK126 and pomalidomide induced specific gene sets involved in B-cell differentiation and apoptosis. Synergistic growth inhibition and B-cell differentiation were further validated in xenograft mouse models. Our collective results provide a molecular basis for the mechanisms underlying the combined therapeutic effects of PRC2 inhibitors and pomalidomide on EZH2-mutated DLBCL.

Download Full-text

MicroRNA Signatures In B-Cell Lymphomas

Blood ◽

10.1182/blood.v116.21.4155.4155 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4155-4155

Author(s):

Lorena Di Lisio ◽

Margarita Sanchez-Beato ◽

Gonzalo Gomez-Lopez ◽

Maria E. E. Rodriguez ◽

Santiago Montes-Moreno ◽

...

Keyword(s):

Cell Differentiation ◽

B Cell ◽

Burkitt Lymphoma ◽

Gene Expression Regulation ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphoid Tissues ◽

Molecular Features ◽

Lymphoma Type

Abstract Abstract 4155 Beyond the conventional criteria of lymphoma classification (integrated clinical, morphological, immunophenotypic, and molecular features) additional markers are still required for a more precise differential diagnosis and a better understanding of lymphoma pathogenesis. MicroRNAs (miRNA) are non-coding small RNAs that play an important role in gene expression regulation, contributing to cell differentiation and tumorigenesis. Specifically, miRNAs have been already described to play a relevant role in B cell differentiation, and in some cases proposed to constitute lymphoma-type specific markers and possible therapeutic targets. We explore the potential diagnostic application of miRNA expression in a large series of 147 cases including all B-cell non-Hodgkin lymphomas (NHL) major types and appropriate controls. As an example of a practical application, data were also used to identify miRNAs differentially expressed when comparing Burkitt Lymphoma (BL) and Diffuse Large B-Cell Lymphoma (DLBCL) in paraffin-embedded samples. Each lymphoma type (BL, CLL, DLBCL, FL, MCL, MZL/MALT, NMZL and SMZL) was compared to the whole series of NHL by Significant Analysis of Microarray (SAM) method. The analysis identified a set of 128 characteristic miRNAs (FDR<0.01 and Fold change >1.5 log2). All lymphoma types were characterized by specific miRNA signatures, reflecting cell of origin and/or discrete oncogene alterations. Of interest is also the comparison with reactive lymphoid tissues, since it revealed a specific B-cell lymphoma miRNA profile, which includes a cluster of downregulated miRNAs, such as let7 family, miR-1 and miR-200 family. Burkitt Lymphoma was also directly compared to DLBCL, and 43 miRNA selected by SAM analysis were studied in a new series of 28 BL and 43 DLBCL samples using quantitative RT-PCRIn this second step, the differential expression of a set of 19 miRNAs was confirmed between BL and DLBCL. (FDR < 0.05 after t-test (limma)). These findings expand the potential diagnostic markers in lymphoma diagnosis and provide useful information on lymphoma pathogenesis. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

A case of primary gastric diffuse large B-cell lymphoma occurring in chronic myeloid leukemia

OncoTargets and Therapy ◽

10.2147/ott.s212838 ◽

2019 ◽

Vol Volume 12 ◽

pp. 5917-5923 ◽

Cited By ~ 2

Author(s):

Zhimei Cai ◽

Shuo Liu ◽

Jie Zi ◽

Jinlong Ma ◽

Zheng Ge

Keyword(s):

Chronic Myeloid Leukemia ◽

B Cell ◽

Myeloid Leukemia ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Download Full-text

Venetoclax for the treatment of newly diagnosed acute myeloid leukemia in patients who are ineligible for intensive chemotherapy

Therapeutic Advances in Hematology ◽

10.1177/2040620719882822 ◽

2019 ◽

Vol 10 ◽

pp. 204062071988282 ◽

Cited By ~ 10

Author(s):

Guillaume Richard-Carpentier ◽

Courtney D. DiNardo

Keyword(s):

Clinical Trials ◽

Acute Myeloid Leukemia ◽

Adverse Events ◽

B Cell ◽

Drug Administration ◽

Myeloid Leukemia ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Intensive Chemotherapy ◽

Acute Myeloid

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a globally poor outcome, especially in patients ineligible for intensive chemotherapy. Until recently, therapeutic options for these patients included low-dose cytarabine (LDAC) or the hypomethylating agents (HMA) azacitidine and decitabine, which have historically provided only short-lived and modest benefits. The oral B-cell lymphoma 2 inhibitor, venetoclax, Venetoclax, an oral B-cell lymphoma 2 (BCL2) inhibitor, is now approved by the USA Food and Drug Administration (FDA) in combination with LDAC or HMA in older AML patients ineligible for intensive chemotherapy. Is now approved by the US Food and Drug Administration for this indication. In the pivotal clinical trials evaluating venetoclax either in combination with LDAC or with HMA, the rates of complete remission (CR) plus CR with incomplete hematological recovery were 54% and 67%, respectively and the median overall survival (OS) was 10.4 months and 17.5 months, respectively, comparing favorably with outcomes in clinical trials evaluating single-agent LDAC or HMA. The most common adverse events with venetoclax combinations are gastrointestinal symptoms, which are primarily low grade and easily manageable, and myelosuppression, which may require delays between cycles, granulocyte colony-stimulating factor (G-CSF) administration, or decreased duration of venetoclax administration per cycle. A bone marrow assessment after the first cycle of treatment is critical to determine dosing and timing of subsequent cycles, as most patients will achieve their best response after one cycle. Appropriate prophylactic measures can reduce the risk of venetoclax-induced tumor lysis syndrome. In this review, we present clinical data from the pivotal trials evaluating venetoclax-based combinations in older patients ineligible for intensive chemotherapy, and provide practical recommendations for the prevention and management of adverse events associated with venetoclax.

Download Full-text

Aggressive large B-cell lymphoma with plasma cell differentiation: immunohistochemical characterization of plasmablastic lymphoma and diffuse large B-cell lymphoma with partial plasmablastic phenotype

Haematologica ◽

10.3324/haematol.2009.016113 ◽

2010 ◽

Vol 95 (8) ◽

pp. 1342-1349 ◽

Cited By ~ 82

Author(s):

S. Montes-Moreno ◽

A.-R. Gonzalez-Medina ◽

S.-M. Rodriguez-Pinilla ◽

L. Maestre ◽

L. Sanchez-Verde ◽

...

Keyword(s):

Cell Differentiation ◽

B Cell ◽

Plasma Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Plasmablastic Lymphoma ◽

Plasma Cell Differentiation ◽

Large B Cell Lymphoma ◽

Large B Cell

Download Full-text

ATRA-induced HL-60 myeloid leukemia cell differentiation depends on the CD38 cytosolic tail needed for membrane localization, but CD38 enzymatic activity is unnecessary

Experimental Cell Research ◽

10.1016/j.yexcr.2010.12.003 ◽

2011 ◽

Vol 317 (7) ◽

pp. 910-919 ◽

Cited By ~ 18

Author(s):

Johanna Congleton ◽

Hong Jiang ◽

Fabio Malavasi ◽

Hening Lin ◽

Andrew Yen

Keyword(s):

Cell Differentiation ◽

Enzymatic Activity ◽

Myeloid Leukemia ◽

Leukemia Cell ◽

Membrane Localization ◽

Myeloid Leukemia Cell

Download Full-text

Mediastinal lymphoma of clear cell type is a tumor corresponding to terminal steps of B cell differentiation

Blood ◽

10.1182/blood.v69.4.1087.1087 ◽

1987 ◽

Vol 69 (4) ◽

pp. 1087-1095 ◽

Cited By ~ 105

Author(s):

P Moller ◽

G Moldenhauer ◽

F Momburg ◽

B Lammler ◽

M Eberlein-Gonska ◽

...

Keyword(s):

Cell Differentiation ◽

B Cell ◽

Clear Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

B Cell Differentiation ◽

Mediastinal Tumors ◽

Hla Dr ◽

Mediastinal Lymphoma ◽

Predominantly Female

Abstract This article reports eight primary mediastinal tumors occurring in young adults (19 to 43 years, mean 29.4 years), predominantly female (six of eight) adults. Most patients responded badly to aggressive therapy. Progression is presently noted in one patient; five patients died 10, 11, 13, 18, and 22 months after diagnosis. No patient developed leukemia. The tumors were highly proliferative, had a diffuse growth pattern, and comprised clear cells of variable size. They could not be classified histologically, but could, however, be immunohistologically characterized as B cell lymphomas. In all cases, the immunophenotype was LC+, cALLa-, CD19+, CD20+, CD21-, Ig (surface/cytoplasm)-, and PC-1+. In addition, the neoplastic cells exhibited variable defects in the expression of HLA-A,B,C and HLA-DR and inconstant expression of other B cell-restricted/associated antigens. This combination of immunophenotypical and clinical features suggests that the mediastinal clear cell lymphoma (MCCL) is a previously undescribed type of B cell lymphoma corresponding to the terminal steps of B cell differentiation.

Download Full-text