Memorial Hospital Research Laboratories // Human Oncology & Pathogenesis Program

Ross L. Levine, MD

The focus of the Levine lab is to improve our understanding of the genetic basis of myeloid malignancies, with a specific focus on the role of oncogenic disease alleles in the pathogenesis of myeloproliferative neoplasms (MPN) and acute myeloid leukemia (AML).

As a postdoctoral fellow in Gary Gilliland’s lab, Dr. Levine used high-throughput sequence analysis of the tyrosine kinome to identify JAK2V617F and MPLW515L in the majority of MPN patients. More recently Dr. Levine’s lab has identified inherited disease alleles relevant to MPN and AML pathogenesis and characterized the effects of targeted therapies on signaling and outcome in MPN mouse models. Dr. Levine’s current efforts are focused on the following areas:

Identification of inherited and acquired disease alleles in MPN pathogenesis
Investigation of the role of different signaling pathways in hematopoietic transformation by activating mutations in JAK2 and MPL
Characterization of the effects of targeted therapies in MPN models and patient samples, and elucidation of the mechanisms of resistance MPN therapies using in vitro systems in order to develop additional novel therapies for MPN patients
Elucidation of the role of mutations in epigenetic modifiers, which impact methylation and chromatin state, in MPN/AML pathogenesis and therapeutic response

Publications

Kilpivaara O, Mukherjee S, Schram AM, Wadleigh M, Mullally A, Ebert BL, Bass A, Marubayashi S, Heguy A, Garcia-Manero G, Kantarjian H, Offit K, Stone RM, Gilliland DG, Klein RJ, Levine RL. A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms. Nat Genet. 2009 Apr;41(4):455-9. doi: 10.1038/ng.342. Epub 2009 Mar 15.

Moran-Crusio K, Reavie L, Shih A, Abdel-Wahab O, Ndiaye-Lobry D, Lobry C, Figueroa ME, Vasanthakumar A, Patel J, Zhao X, Perna F, Pandey S, Madzo J, Song C, Dai Q, He C, Ibrahim S, Beran M, Zavadil J, Nimer SD, Melnick A, Godley LA, Aifantis I, Levine RL. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell. 2011 Jul 12;20(1):11-24. doi: 10.1016/j.ccr.2011.06.001. Epub 2011 Jun 30.

Patel JP, Gönen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, Van Vlierberghe P, Dolgalev I, Thomas S, Aminova O, Huberman K, Cheng J, Viale A, Socci ND, Heguy A, Cherry A, Vance G, Higgins RR, Ketterling RP, Gallagher RE, Litzow M, van den Brink MR, Lazarus HM, Rowe JM, Luger S, Ferrando A, Paietta E, Tallman MS, Melnick A, Abdel-Wahab O, Levine RL. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012 Mar 22;366(12):1079-89. doi: 10.1056/NEJMoa1112304. Epub 2012 Mar 14.

Koppikar P, Bhagwat N, Kilpivaara O, Manshouri T, Adli M, Hricik T, Liu F, Saunders LM, Mullally A, Abdel-Wahab O, Leung L, Weinstein A, Marubayashi S, Goel A, Gönen M, Estrov Z, Ebert BL, Chiosis G, Nimer SD, Bernstein BE, Verstovsek S, Levine RL. Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy. Nature. 2012 Sep 6;489(7414):155-9. doi: 10.1038/nature11303.

Abdel-Wahab O, Adli M, LaFave LM, Gao J, Hricik T, Shih AH, Pandey S, Patel JP, Chung YR, Koche R, Perna F, Zhao X, Taylor JE, Park CY, Carroll M, Melnick A, Nimer SD, Jaffe JD, Aifantis I, Bernstein BE, Levine RL. ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell. 2012 Aug 14;22(2):180-93. doi: 10.1016/j.ccr.2012.06.032.

Related Cancer & Treatment Information

Leukemias