Ginger Price.  A basic helix-loop-helix (bHLH) transcription factor  These domains are essential for protein dimerization and DNA binding

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Presentation transcript:

Ginger Price

 A basic helix-loop-helix (bHLH) transcription factor  These domains are essential for protein dimerization and DNA binding

 E2A encodes several transcription factors via alternative splicing of precursor mRNA.

 E2A null mice are viable and fertile!

T(1;19)(q23;p13) T(17;19)(q21-22;p23)

Hunger S P. Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis. Blood. 1996;87:1211–1224.

 Estimated ◦ New cases: 44, 270 ◦ Deaths: 21,710

Large: NK cells Small: T cells B cells

 Most common cancer in children  1/29,000 each year

 Chemotherapy  85% - 5 years or more

 Altura, Rachel A., Takeshi Inukai, Richard A. Ashmun, Gerard P. Zambetti, Martine F. Roussel, and A. Thomas Look The Chimeric E2A-HLF Transcription Factor Abrogates p53-Induced Apoptosis in Myeloid Leukemia Cells. Blood 92:  Bhalla, Savita, Spaulding, Christina, Brumbaugh, Rachel L., Zagort, Derek E., Massari, Mark E., Murre, Cornelis, Kee, Barbara L. Differential Roles for the E2A Activation Domains in B Lymphocytes and Macrophages. J Immunol :  Ferramdo AA, Look AT (2005). Hematology, In: Hoffman (ed). Pathobiology of Acute Lymphoblastic Leukemia, 4th edn, chapter  Herblot, Sabine, Aplan, Peter D., Hoang, Trang. Gradient of E2A Activity in B-Cell Development. Mol. Cell. Biol :  Hunger S P. Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis. Blood. 1996;87:1211–1224.  Hunger SP, Sun T, Boswell AF, Carroll AJ, McGavran L. Hyperdiploidy and E2A-PBX1 fusion in an adult with t(1;19)+ acute lymphoblastic leukemia: case report and review of the literature. Genes Chromosomes Cancer Dec;20(4):  Kamps, M P, Look, A T, Baltimore, D. The human t(1;19) translocation in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with differing transforming potentials. Genes Dev :  Lietz, Andreas, Martin Janz, Mikael Sigvardsson, Franziska Jundt, Bernd Dörken, Stephan Mathas (2007) Loss of bHLH transcription factor E2A activity in primary effusion lymphoma confers resistance to apoptosis. British Journal of Haematology 137 (4), 342–348  Murre Lab Web Site. University of California at San Diego. biology.ucsd.edu/labs/murre/NewFiles/research.html  Sykes, David B., Kamps, Mark P. E2a/Pbx1 Induces the Rapid Proliferation of Stem Cell Factor-Dependent Murine Pro-T Cells That Cause Acute T-Lymphoid or Myeloid Leukemias in Mice. Mol. Cell. Biol :  Wikstrom, Ingela, Forssell, Johan, Goncalves, Mario, Colucci, Francesco, Holmberg, Dan. E2-2 Regulates the Expansion of Pro-B Cells and Follicular versus Marginal Zone Decisions. J Immunol :