Dr. Michael Andreeff

Regular Member

The University of Texas MD Anderson Cancer Center
Departments of Leukemia and Stem Cell Transplantation & Cellular Therapy

Research Interests:

• Leukemia molecular and cell biology
• Leukemia stem cells
• Leukemia therapy
• Leukemia and solid tumor microenvironment
• Mesenchymal stem cells
• Hematopoietic stem cells
• Hypoxia
• Cell signaling
• Apoptosis

Molecular Hematology and Therapy is a Section in the Leukemia Department with close links to the Department of Stem Cell Transplantation and Cellular Therapy. Focus is on leukemia research, with emphasis on apoptosis regulation, signaling pathways (FLT3-Ras-Ras-MEK-ERK, PI3K-AKT-mTOR, STAT3 and 5) , their links to apoptosis and autophagy and to the micro-environment. The Section encompasses 12 faculty and 25 additional scientists and includes the MD Anderson CCSG-sponsored "Flow Cytometry/Cell Sorting/Confocal Microscopy" Core Lab. Investigations of apoptosis and cell signaling pathways resulted in the development of new drug targets including Bcl-2, BclX_L, McL-1, MDM2/p53, inhibitors-of-apoptosis proteins (XIAP, Survivin, cIAP1,2), FLT3-ITD, AKT/mTOR and pERK, which we have moved from basic to translational research into trials. We emphasize that successful drug development has to target the right cells ("primary stem cells", not cell line cells) in the physiological, i.e. hypoxic tumor microenvironment. The group has major expertise in the study of hematopoietic and solid tumor systems . We were first to report the critical role of bone marrow-derived MSC (mesenchymal stem cells) in the formation of tumor stroma and have developed therapies that deliver therapeutic genes into tumors by way of MSC. Several transgenic and knock-out mouse models have been developed to provide a better understanding of tumor- and microenvironmental molecular biology. Leukemia cells with most relevant translocations and mutations have been generated in collaboration with CSH. Major efforts are ongoing to disrupt interactions between leukemia/tumor stem cells and their micro-environment (targeting CXCR4, VLA-4, CD44). The first fully human system forming bone and bone marrow has been developed in immuno-deficient NOG mice, whose components can be genetically modified. Finally, in collaborations with pharmaceutical corporations and biotechnology companies, drugs are being developed targeting genes, RNAs and proteins of interest.

Selected Publications:

Battula VL, Evans KW, Hollier BG, Shi Y, Marini FC, Ayyanan A, Wang RY, Brisken C, Guerra R, Andreeff M, Mani SA. Epithelial-mesenchymal transition-derived cells exhibit multi-lineage differentiation potential similar to mesenchymal stem cells. Stem Cells 28(8):1435-1445, 8/2010. e-Pub 6/2010

Kojima K, Konopleva M, Samudio IJ, Shikami M, Cabreira-Hansen M, McQueen T, Ruvolo V, Tsao T, Zeng Z, Vassilev LT, Andreeff M. MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy. Blood 106(9):3150-3159, 2005. PMID: 16014563

Konopleva M, Contractor R, Tsao T, Samudio I, Ruvolo PP, Kitada S, Deng X, Zhai D, Shi Y-X, Sneed T, Verhaegen M, Soengas M, Ruvolo VR, McQueen T, Schober WD, Watt JC,  Jiffar T, Ling X, Marini FC, Harris D, Dietrich M, Estrov Z, McCubrey J, May WS, Reed JC, Andreeff M. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell 10:375-388, 2006. PMID 17097560

Kornblau SM, Womble M, Qiu YH, Jackson E, Chen W, Konopleva M, Estey EH, Andreeff M. Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia. Blood 108:2358-2365, 2006. PMID 16763210

Milella M, Konopleva M, Precupanu CM, Tabe Y, Ricciardi MR, Gregorj C, Collins SJ, Carter BZ, d’Angelo C, Petrucci MT, Foa R, Cognetti F, Tafuri A, Andreeff M. MEK blockade converts AML differentiating response to retinoids into extensive apoptosis. Blood 109(5):2121-2129, 2007. PMID: 17077328

Ling X, Konopleva M, Zeng Z, Ruvolo V, Stephens LC, Schober W, McQueen T, Dietrich M, Madden TL, Andreeff M. The novel triterpenoid C-28 methyl ester of 2-cyano-3, 12-dioxoolen-1, 9-dien-28-oic acid inhibits metastatic murine breast tumor growth through inactivation of STAT3 signaling. Cancer Res 67: 4210-4218, 2007. PMID 17483332

Kojima K, Konopleva M, Tsao T, Nakakuma H, Andreeff M. Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia. Blood 112(7):2886-2895, 2008. PMID: 18633130

Andreeff M, Ruvolo V, Gadgil S, Zeng C, Coombes K, Chen W, Kornblau S, Baron AE, Drabkin HA. HOX expression patterns identify a common signature for favorable AML. Leukemia 22:2041-2047, 2008. PMID 18668134

Zhang W, Konopleva M, Shi YX, McQueen T, Harris D, Ling X, Estrov Z, Quintas-Cardama A, Small D, Cortes J, Andreeff M. Mutant FLT3: a direct target of sorafenib in acute myelogenous leukemia. J Natl Cancer Inst 100(3):184-198, 2008. PMID 18230792

Samudio I, Fiegl M, Andreeff M. Mitochondrial uncoupling and the Warburg effect: molecular basis for the reprogramming of cancer cell metabolism. Cancer Res 69:2163-2166, 2009. PMID 19258498

Kidd S, Spaeth E, Dembinski JL, Dietrich M, Watson K, Klopp A, Battula L, Weil M, Andreeff M, Marini FC. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescence imaging. Stem Cells 27:2614-2623, 2009. PMID 19650040

Ling X, Marini F, Konopleva M, Schober W, Shi Y, Burks J, Clise-Dwyer K, Wang R-Y, Zhang W, Yuan X, Lu H, Caldwell L, Andreeff M. Mesenchymal stem cells overexpressing IFN-beta inhibit breast cancer growth and metastases through Stat3 signaling in a syngeneic tumor model. Cancer Microenvironment 3(1):83-95, 12/2010. PMCID: PMCPMC2990497.

Carter BZ, Mak DH, Morris SJ, Borthakur G, Estey E, Byrd AL, Konopleva M, Kantarjian H, Andreeff M. XIAP antisense oligonucleotide (AEG35156) achieves target knockdown and induces apoptosis preferentially in CD34+38- cells in a phase 1/2 study of patients with relapsed/refractory AML. Apoptosis 16(1):67-74, 1/2011. e-Pub 10/2010.

Additional Publications

Program Affiliations:

Program in Cancer Biology

Program in Experimental Therapeutics