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We are studying the biology of infant-leukemia to identify novel therapeutic approaches to treat this disease. Infants with leukemia face an exceptionally grim prognosis because the pathogenesis of the disease is different than that seen in older children. Majority of leukemia in infants involve translocations of the MLL gene on chromosome 11q23. We are studying experimental models of MLL-rearranged leukemia in the laboratory to discover biological pathways that are dysregulated in the leukemic cells. In knock-in MLL-AF9 mice, we have identified several genes that are abnormally upregulated in hematopoietic cells compared to corresponding wild type cells. These genes and pathways are also up-regulated in leukemia cells of human patients. We are now studying the role of these activated genes in the pathogenesis of leukemia.
Unnisa Z, Clark JP, Roychoudhury J, Thomas E, Tessarollo L, Copeland NG, Jenkins NA, Grimes HL, Kumar AR. Meis1 preserves hematopoietic stem cells in mice by limiting oxidative stress. Blood. 2012.
Bindels EM, Havermans M, Lugthart S, Erpelinck C, Wocjtowicz E, Krivtsov AV, Rombouts E, Armstrong SA, Taskesen E, Haanstra JR, Beverloo HB, Döhner H, Hudson WA, Kersey JH, Delwel R, Kumar AR. EVI1 is critical for the pathogenesis of a subset of MLL-AF9 rearranged AMLs.Blood. Jun 14;119(24):5838-49. 2012.
Kumar AR, Yao Q, Li Q, Sam TN and Kersey JH. t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL. Leukemia Research. 35(3):305-9. 2010.
Kumar AR, Sarver A, Wu B and Kersey JH. Meis1 maintains ‘stemness’ signature in MLL-AF9 leukemia. Blood. Apr 29;115(17):3642-3. 2010.
Kumar AR, Li Q, Hudson WA, Chen W, Yao Q, Sam TN, Wu B, Lund EA, Kowal BJ and Kersey JH. A role for MEIS1 in MLL-fusion gene leukemia. Blood. Feb 19;113(8):1756-8. 2009.
Chen W, Kumar AR, Hudson WA, Li Q, Wu B, Staggs RA, Lund EA, Sam TN and Kersey JH. Malignant transformation initiated by Mll-AF9: Gene dosage and critical target cells. Cancer Cell. May; 13: 432-440. 2008.
Ashish Kumar, MD, PhDDivision of Bone Marrow Transplantation and Immune DeficiencyCancer and Blood Diseases Institute
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