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The role of E2A in B cell chronic lymphocytic leukemia
Author(s) -
Kardava Lela,
Foon Kenneth A.,
Borghesi Lisa
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1079.6
Subject(s) - chronic lymphocytic leukemia , b cell , apoptosis , dapi , cell cycle , biology , flow cytometry , downregulation and upregulation , transfection , cancer research , cell growth , leukemia , microbiology and biotechnology , immunology , cell culture , antibody , gene , biochemistry , genetics
E2A is a major regulator of B cell development and function, but nothing is known about the role of this transcription factor in B cell chronic lymphocytic leukemia (B‐CLL), which is a cancer of mature B cell origin. The aim of the present study was to examine the role of E2A in the pathogenesis of CLL. First we studied the expression of E2A in CLL cells and normal human B subsets by intracellular staining and flow cytometry. We show that E2A is normally expressed at high levels in the precursor stage of human B cell development in the bone marrow and is downregulated in mature B subsets. In contrast, E2A expression in CLL cells is upregulated compared with normal mature B subsets. Further we determined whether small interfering RNA (siRNA) mediated inhibition of E2A protein levels restores normal cell cycling or induces apoptosis of CLL cells. We transfected CLL cells with E2A specific siRNA using Nucleofection. We were able successfully perform this approach on primary CLL cells. Then we examined cell cycle status by staining with DyeCycle Violet reagent and the level of apoptosis using Annexin/DAPI staining. Our results showed that E2A downregulation in CLL cells was sufficient to promote cell cycle progression in 50% of cases and induced apoptosis in all cases studied. We conclude that overexpression of E2A is likely to play a pathogenetic role in B‐CLL and may be a potential target in the treatment of this disease. NIH/NIAMS, USIDNET