The Hematologic Malignancies Program (HMP) is a multidisciplinary, collaborative group of basic, translational, and clinical investigators that includes 74 members (46 primary, 28 associate) from 11 departments. The HMP is led by Robert Z. Orlowski, a laboratory-based physician-scientist with expertise in plasma cell biology, protein homeostasis, and drug resistance; Michael Andreeff, a laboratory-based physician-scientist focusing on lymphoid and myeloid cell biology, apoptotic signaling, and stem cell biology; and Hagop M. Kantarjian, a clinician-scientist who is an authority on clinical and translational leukemia biology. Members of the HMP pursue the goal of enhancing our understanding of the pathobiology of hematologic malignancies, and leveraging this new knowledge to develop effective personalized, targeted treatment strategies that ultimately will enable us to cure all patients with these diseases. To achieve this goal, the HMP has the following specific aims:
Aim 1 : To study the epigenome and identify novel drivers of malignant disease and to develop therapies targeted to these features;
Aim 2 : To develop antibodies, vaccines, and adoptive cellular immunotherapies that boost immune recognition and eliminate malignant cells;
Aim 3 : To define microenvironmental influences on tumor biology and drug resistance that modulate biomarkers and regulate chemosensitivity;
and Aim 4 : To validate novel therapies in preclinical models and translate them in a rational, biomarker-driven approach to maximize their impact upon patient outcomes. Program annual direct peer-reviewed funding totals $6.7M, of which $3.8M (57%) is from the National Cancer Institute, including a SPORE in Leukemia. The HMP is leveraging strategic industry alliances and the MD Anderson Moon Shots Program to enhance the breadth of investigator-initiated translational studies and to strengthen understanding of basic biology of these malignancies. Over the last six years, HMP investigators have authored more than 2017 publications where 1126 (56%) represent intra-programmatic collaborations, 545 (27%) represent inter-programmatic collaborations, and 1192 (59%) represent inter- institutional collaborations. Fifty-one percent of publications have appeared in journals with IF >5 and 20% in journals with IF >10, including Cancer Cell, N Engl J Med, and Lancet Oncol. Program members utilized 14 shared resources. During the past grant period, program members contributed significantly to regulatory approval of multiple agents for hematologic malignancies, including small-molecule inhibitors of Bruton tyrosine kinase, BCR/ABL, B-cell CLL/lymphoma 2, and Janus kinase 2 as well as immunotherapies targeting CD19 and other moieties.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee I - Transistion to Independence (NCI)
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University of Texas MD Anderson Cancer Center
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Liu, Yihua; Weber, Zachary; San Lucas, F Anthony et al. (2018) Assessing inter-component heterogeneity of biphasic uterine carcinosarcomas. Gynecol Oncol 151:243-249
Joint Head and Neck Radiotherapy-MRI Development Cooperative (2018) Dynamic contrast-enhanced magnetic resonance imaging for head and neck cancers. Sci Data 5:180008
Jensen, Garrett; Tao, Randa; Eng, Cathy et al. (2018) Treatment of primary rectal adenocarcinoma after prior pelvic radiation: The role of hyperfractionated accelerated reirradiation. Adv Radiat Oncol 3:595-600
Staffas, Anna; Burgos da Silva, Marina; Slingerland, Ann E et al. (2018) Nutritional Support from the Intestinal Microbiota Improves Hematopoietic Reconstitution after Bone Marrow Transplantation in Mice. Cell Host Microbe 23:447-457.e4
Boddu, Prajwal; Borthakur, Gautam; Koneru, Mythili et al. (2018) Initial Report of a Phase I Study of LY2510924, Idarubicin, and Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia. Front Oncol 8:369
Takahashi, Nobuaki; Chen, Hsing-Yu; Harris, Isaac S et al. (2018) Cancer Cells Co-opt the Neuronal Redox-Sensing Channel TRPA1 to Promote Oxidative-Stress Tolerance. Cancer Cell 33:985-1003.e7
Garg, Rachana; Blando, Jorge M; Perez, Carlos J et al. (2018) COX-2 mediates pro-tumorigenic effects of PKC? in prostate cancer. Oncogene 37:4735-4749
Flinn, Ian W; O'Brien, Susan; Kahl, Brad et al. (2018) Duvelisib, a novel oral dual inhibitor of PI3K-?,?, is clinically active in advanced hematologic malignancies. Blood 131:877-887
Subbiah, Ishwaria M; Tang, Chad; Rao, Arvind et al. (2018) Older adults in phase I clinical trials: a comparative analysis of participation and clinical benefit rate among older adults versus middle age and AYA patients on phase I clinical trials with VEGF/VEGFR inhibitors. Oncotarget 9:28842-28848
Daver, Naval; Boddu, Prajwal; Garcia-Manero, Guillermo et al. (2018) Hypomethylating agents in combination with immune checkpoint inhibitors in acute myeloid leukemia and myelodysplastic syndromes. Leukemia 32:1094-1105

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