Yuri Pekarsky, PhD, Affiliate
College of Medicine
Molecular Virology, Immunology & Medical Genetics
Res Asst Professor
Molecular Biology and Cancer Genetics
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, T-Cell, Neoplasms, Leukemia, Disease Models, Animal, Lymphoma, T-Cell, Chromosome Aberrations, Cell Transformation, Neoplastic, Trisomy, Lung Neoplasms
Mature T-cell leukemia commonly shows chromosomal rearrangements at 14q32.1 including translocations t(14;14)(q11;q32), t(7;14)(q35;q32) and inversions inv(14)(q11;q32). The investigation of the locus in question at 14q32.1 resulted in the identification of two related genes named TCL1 and TCL1b. Both genes are activated in T-PLL/T-CLL by the chromosomal aberrations mentioned above. Recently we discovered that biochemically, TCL1 works as a co-factor of the Akt kinase, a key regulator of antiapoptotic and proliferative signals. Tcl1 interacts physically with Akt, increases its kinase activity and facilitates its transport to the nucleus. The pathogenesis of T-PLL/T-CLL may also involve Nur77, a T-cell transcription factor required for T-cell receptor (TCR) mediated apoptosis. In our recent publication we demonstrate that Akt phosphorylates Nur77, thereby blocking its DNA-binding ability and rendering the transcription factor inactive. Currently we concentrate on studying of downstream events of this pathway as well as on the identification new pathways involving Tcl1 and Akt.