Research Assistant Professor
Department of Cancer Biology and Genetics
Human Cancer Genetics Program
1090 Biomedical Research Tower
460 W 12th Ave
Columbus, OH 43210
Ph. (614) 292-4134
Dr. Pekarsky’s research is focused on the investigation of function of TCL1 oncogene. 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. Tcl1 expression is also abnormally induced in B-cell chronic lymphocytic leukemia (B-CLL), the most common leukemia in the world. 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 and B-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.
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Palamarchuk A, Yan PS, Zanesi N, Wang L, Rodrigues B, Murphy M, Balatti V, Bottoni A, Nazaryan N, Alder H, Rassenti L, Kipps TJ, Freitas M, Croce CM, Pekarsky Y. Tcl1 protein functions as an inhibitor of de novo DNA methylation in B-cell chronic lymphocytic leukemia (CLL). PNAS, 109:2555-60, 2012
Balatti V, Bottoni A, Palamarchuk A, Alder H, Rassenti LZ, Kipps TJ, Pekarsky Y, Croce CM. NOTCH1 mutations in CLL associated with trisomy 12. Blood, 119:329-31, 2012
Gaudio E, Spizzo R, Paduano F, Luo Z, Efanov A, Palamarchuk A, Leber A, Kaou M, Zanesi N, Bottoni A, Costinean S, Rassenti L, Nakamura T, Kipps T, Aqeilan R, Pekarsky Y, Trapasso F, Croce CM. Tcl1 interacts with Atm and enhances NF-kB activation in hematological malignancies. Blood, 119:180-187, 2012.
Veronese A, Visone R, Consiglio J, Acunzo M, Lupini L, Kim T, Ferracin M, Lovat F, Miotto E, Balatti V, D'Abundo L, Gramantieri L, Bolondi L, Pekarsky Y, Perrotti D, Negrini M, Croce CM. Mutated beta-catenin evades a microRNA-dependent regulatory loop. PNAS, 108:4840-5, 2011. PMC3064338
Havelange V, Pekarsky Y, Nakamura T, Palamarchuk A, Alder H, Rassenti L, Kipps T, Croce CM. IRF4
mutations in chronic lymphocytic leukemia. Blood, 118: 2827-29, 2011.
Voltan R, di Iasio MG, Bosco R, Valeri N, Pekarsky Y, Tiribelli M, Secchiero P, Zauli G.Nutlin-3 Down- regulates the Expression of the Oncogene TCL1 in Primary CLL Cells. Clin Cancer Res. 17:5649-55, 2011.
Santanam U, Zanesi N, Efanov A, Costinean S, Palamarchuk A, Hagan JP, Volinia S, Alder H, Rassenti L, Kipps T, Croce CM, Pekarsky Y. Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression. PNAS, 107:12210-15, 2010. PMC2901490
Palamarchuk A, Efanov A, Nazaryan N, Santanam U, Alder H, Rassenti L, Kipps T, Croce CM, Pekarsky Y. 13q14 deletions in CLL involve cooperating tumor suppressors. Blood, 115:3916-22, 2010
Efanov A, Zanesi N, Nazaryan N, Santanam U, Palamarchuk A, Croce CM, Pekarsky Y. CD5+CD23+ leukemic cell populations in TCL1 transgenic mouse show significantly increased proliferation and Akt phosphorylation. Leukemia, 24:970-5, 2010.
Pekarsky Y, Croce CM. Is miR-29 an oncogene or tumor suppressor in CLL? Oncotarget, 1: 224-227, 2010. PMC2951328
Pekarsky Y, Zanesi N, Croce CM. Molecular basis of CLL. Semin Cancer Biol, 20:370-6, 2010
Zanesi N, Pekarsky Y, Trapasso F, Calin G, Croce CM. MicroRNAs in mouse models in lymphoid malignancies. J Nucl Acids Invest, 1:36-40, 2010