The chronic phase of Chronic Myelogenous Leukemia (CML) is initiated with the formation of the Philadelphia chromosome translocation, and evolves into a fulminant life threatening leukemic syndrome through the acquisition of additional chromosomal rearrangements and mutational changes in the DNA. All of the current therapy is designed to prevent this transition of CML to the more acute phases of the diseases. Since the most reliable predictor of a reduced probability of progression of the disease is the disappearance of the Philadelphia chromosome, the UT MD Anderson CML group has developed several therapeutic programs to generate cytogenetic remissions in CML: Interferon and its combination with the chemotherapeutic agents hydroxyurea, cytosine arabinoside (ara), and homoharringtonine (HHT), growth factor receptor antagonists, the combinations of chemotherapy of daunomycin and high dose cytosine arabinoside (DaraC), Fludarabine, araC, and mitoxantrone (FAM), matched related and unrelated allogeneic bone marrow transplants, collection of peripheral blood diploid progenitor cells following DaraC and FAM, and blood diploid progenitor cells following DaraC and FAM, and autologous bone marrow transplantation with ex vivo and in vivo selection of normal diploid progenitor cells. Because of the success observed already in restoring diploid hematopoiesis in CML patients with these modalities, and the development of molecular assays which are specific for persistent leukemia cells at sensitivities ranging from 1 CML cell/100 normal cells to 1 CML cell in 100,000 normal cells, we are proposing to use, the molecular assays of FISH, PCR, P210 assays and monoclonal antibody assays for rare immunophenotypes unique to the CML blasts to trigger the initiation of additional therapeutic programs prior to the time of cytogenetic or clinical relapse, when the level of CML cells detected by these assays is increasing, albeit beneath the level of clinical detection. Since the persistence of neoplastic myeloid cells detected by several of these assays is predictive of adverse clinical outcome, we are proposing to evaluate the potential benefit of intervening early to prevent relapse. This program will also encompass the development of novel therapeutic interventions which are designed to correct the biological abnormalities recently uncovered in this disease, further clarify the molecular basis of progression and therapeutic resistance in this disease, and develop more effective therapeutic interventions for patients already at the more advanced stages of the disease.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (SRC (K1))
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Wu, Roy S
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University of Texas MD Anderson Cancer Center
Other Basic Sciences
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United States
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Ruvolo, Peter P; Ruvolo, Vivian R; Burks, Jared K et al. (2018) Role of MSC-derived galectin 3 in the AML microenvironment. Biochim Biophys Acta Mol Cell Res 1865:959-969
Cortes, Jorge E; Gambacorti-Passerini, Carlo; Deininger, Michael W et al. (2018) Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. J Clin Oncol 36:231-237
Sasaki, Koji; Kantarjian, Hagop; O'Brien, Susan et al. (2018) Prediction for sustained deep molecular response of BCR-ABL1 levels in patients with chronic myeloid leukemia in chronic phase. Cancer 124:1160-1168
Gambacorti-Passerini, Carlo; Cortes, Jorge E; Lipton, Jeff H et al. (2018) Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study. Haematologica 103:1298-1307
Boddu, Prajwal; Shah, Abdul Rashid; Borthakur, Gautam et al. (2018) Life after ponatinib failure: outcomes of chronic and accelerated phase CML patients who discontinued ponatinib in the salvage setting. Leuk Lymphoma 59:1312-1322
Kornblau, Steven M; Ruvolo, Peter P; Wang, Rui-Yu et al. (2018) Distinct protein signatures of acute myeloid leukemia bone marrow-derived stromal cells are prognostic for patient survival. Haematologica 103:810-821
Zhang, Weiguo; Ly, Charlie; Ishizawa, Jo et al. (2018) Combinatorial targeting of XPO1 and FLT3 exerts synergistic anti-leukemia effects through induction of differentiation and apoptosis in FLT3-mutated acute myeloid leukemias: from concept to clinical trial. Haematologica 103:1642-1653
Alhuraiji, Ahmad; Kantarjian, Hagop; Boddu, Prajwal et al. (2018) Prognostic significance of additional chromosomal abnormalities at the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors. Am J Hematol 93:84-90
Ishizawa, Jo; Nakamaru, Kenji; Seki, Takahiko et al. (2018) Predictive Gene Signatures Determine Tumor Sensitivity to MDM2 Inhibition. Cancer Res 78:2721-2731
Boddu, Prajwal; Benton, Christopher B; Wang, Wei et al. (2018) Erythroleukemia-historical perspectives and recent advances in diagnosis and management. Blood Rev 32:96-105

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