The overall goal of this Program Project is to develop an understanding of the biological and molecular biological phenomena which underlie neoplastic disease. To this end we will use the myeloid disorders as model systems and will carefully study normal myelopoiesis, preleukemia, and acute leukemia in order to develop an understanding of the differences among these different states and of the phenomena associated with the development of neoplastic disease. The studies in Project I are designed to precisely characterize myeloid cells with respect to cell lineage and level of maturation using morphologic criteria, histochemical stain, cell surface marker analysis, and electron microscopy. The biologic characteristics of preleukemic and leukemic cells in vivo will be defined by the cell cycle and differentiation studies of Project II. Project III is devoted to studying leukemic cell proliferation and differentiation under controlled conditions in vitro. The effect of environmental conditions and hemopoietins will be studied as well. Projects IV and V are devoted to defining the genic phenomena which underlie the biologic phenomena defined in Project 1, II, and III. the evolution Studies performed during of preleukemia to leukemia will provide insight into the development of acute leukemia. Project VII will provide the cytogenetic underpinnings of the proto-oncogene studies and will add data which will compliment more developed in Project I. Project VI is directed towards developing hybrid therapies by combining bioactive reagents with cytotoxic agents and to providing reagents useful for developing new in vitro drug sensitivity assays and for studying proto oncogene expression at the level of the single cell. By integrating the biological and molecular biological data with observations during and after both cytotoxic and bioactive therapies an understanding will be developed of the phenomena associated with response/unresponse to-therapy and of the likely course of the diseases being studied. Intensive studies of bioactive agents will be directed towards understanding their effects so that these potentially useful therapies can be introduced into our therapeutic armamentarium.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
7P01CA041285-05
Application #
3093895
Study Section
(SRC)
Project Start
1985-09-30
Project End
1991-11-30
Budget Start
1989-01-09
Budget End
1989-11-30
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Raza, Azra; Qawi, Huma; Mehdi, Murtaza et al. (2004) Translational research in myelodysplastic syndromes. Rev Clin Exp Hematol 8:E2
Preisler, H D; Raza, A; Gopal, V et al. (1994) The study of acute leukemia cells by means of acridine orange staining and flow cytometry. Leuk Lymphoma 13:61-73
Preisler, H D; Banavali, S D; Yin, M et al. (1994) Parallel studies of clonogenic leukaemia cells and the leukaemia cell population as a whole in acute myelogenous leukaemia. Eur J Cancer 30A:1511-6
Preisler, H D; Raza, A; Larson, R et al. (1994) The relationship of the in vivo cell cycle characteristics and treatment outcome in acute myelogenous leukemia to the expression of the FMS and MYC proto-oncogenes. Leuk Lymphoma 14:273-8
Yin, M; Silvestri, F F; Banavali, S D et al. (1993) Clonogenic potential of myeloid leukaemia cells in vitro is restricted to leukaemia cells expressing the CD34 antigen. Eur J Cancer 29A:2279-83
Goldberg, J; Gryn, J; Raza, A et al. (1993) Mitoxantrone and 5-azacytidine for refractory/relapsed ANLL or CML in blast crisis: a leukemia intergroup study. Am J Hematol 43:286-90
Preisler, H; Raza, A (1993) An overview of some studies of chronic myelogenous leukemia: biological-clinical observations and viewing the disease as a chaotic system. Leuk Lymphoma 11 Suppl 1:145-50
Raza, A; Preisler, H D; Li, Y Q et al. (1993) Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia. Am J Hematol 42:359-66
Raza, A; Preisler, H; Lampkin, B et al. (1993) Clinical and prognostic significance of in vivo differentiation in acute myeloid leukemia. Am J Hematol 42:147-57
Preisler, H (1993) Poor prognosis acute myelogenous leukemia. Leuk Lymphoma 9:273-83

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