Abstract

This project involves clinical investigation of strategies to improve results of chemotherapy and biologic treatment of CML.
Aim 1 builds upon the success of the program in defining the activity of interferon-alpha for CML and more recently the combination of interferon and cytarabine. We will test the hypothesis that the combination of interferon-alpha, cytarabine and ATRA improves outcome compared to interferon- alpha/cytarabine treatment.
Aim 2 is directed to evaluation of a decitabine, a novel chemotherapeutic agent with a unique mechanism of action to determine if it an induce significant and durable suppression of the Ph-positive cells in late chronic phase CML and/or in interferon alpha (IFN-A) resistant CML disease. The effects of this agent on DNA methylation will be studied and related to the evaluation of epigenetic alterations in Project 9.
Aims 3 and 4 are directed to evaluating novel biologic agents in patients failing to have a major response to interferon.
Aim 3 develops therapeutic approaches to overcome resistance to interferon-alpha via the inhibition of cellular production of interleukin 1-beta evaluation of interleukin-1 receptor antagonist.
In aim 4, the objective is to identify biologics which improve cytogenetic response to interferon. In a pilot study, the combination of interferon- alpha and GM-CSF has produced marked cytogenetic responses in interferon resistant patients; this combination will be studied in a larger phase II trial to evaluate its potential efficacy. This project interacts extensively with he basic science projects within this proposal, particularly, Project 5 (Molecular Sensitization of p210 Bcr-Abl Positive Cells to Therapy), Project 4 (Stem Cell Prognosticators of Sensitivity & Resistance in CML) and Project 9(Epigenetic Alterations in CML).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA049639-13
Application #
6587810
Study Section
Project Start
2002-04-24
Project End
2003-01-31
Budget Start
Budget End
Support Year
13
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

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
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

Showing the most recent 10 out of 375 publications