Abstract

The process of normal hematopoiesis requires the sequential coordination of many complex events. These include the interaction of stimulatory growth factors with their membrane receptors, generation of the appropriate signal followed by its transduction through the cell membrane and cytoplasm into the nucleus, and finally, DNA synthesis and cell division. Accordingly, it seems reasonable to assume that perturbations in any of these controlled events are likely to result in altered cell growth patterns and possibly in the emergence of cells with a leukemic phenotype, especially in the presence of cumulative alterations in these various components of the proliferative program. As a paradigm of this concept, our proposal centers on the investigation of the role of c-myb in normal and leukemic hematopoiesis because this gene is not only involved in cell cycle regulation, but also appears to affect the generation of the growth signal and its transduction in a cell- type specific manner.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA046782-09
Application #
2330747
Study Section
Pathology B Study Section (PTHB)
Project Start
1988-08-01
Project End
2000-01-31
Budget Start
1997-02-01
Budget End
1998-01-31
Support Year
9
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107

  Publications

Fernandes, M J; Iscove, N N; Gingras, G et al. (2000) Identification and characterization of the gene for a novel C-type lectin (CLECSF7) that maps near the natural killer gene complex on human chromosome 12. Genomics 69:263-70
Fernandes, M J; Finnegan, A A; Siracusa, L D et al. (1999) Characterization of a novel receptor that maps near the natural killer gene complex: demonstration of carbohydrate binding and expression in hematopoietic cells. Cancer Res 59:2709-17
Sevignani, C; Cranston, A; Iozzo, R V et al. (1999) Spontaneous and mutagen-induced transformation of primary cultures of Msh2-/- p53-/- colonocytes. Cancer Res 59:5882-6
Nieborowska-Skorska, M; Wasik, M A; Slupianek, A et al. (1999) Signal transducer and activator of transcription (STAT)5 activation by BCR/ABL is dependent on intact Src homology (SH)3 and SH2 domains of BCR/ABL and is required for leukemogenesis. J Exp Med 189:1229-42
Iozzo, R V; Chakrani, F; Perrotti, D et al. (1999) Cooperative action of germ-line mutations in decorin and p53 accelerates lymphoma tumorigenesis. Proc Natl Acad Sci U S A 96:3092-7
Sevignani, C; Wlodarski, P; Kirillova, J et al. (1998) Tumorigenic conversion of p53-deficient colon epithelial cells by an activated Ki-ras gene. J Clin Invest 101:1572-80
Santra, M; Mann, D M; Mercer, E W et al. (1997) Ectopic expression of decorin protein core causes a generalized growth suppression in neoplastic cells of various histogenetic origin and requires endogenous p21, an inhibitor of cyclin-dependent kinases. J Clin Invest 100:149-57
Bellon, T; Perrotti, D; Calabretta, B (1997) Granulocytic differentiation of normal hematopoietic precursor cells induced by transcription factor PU.1 correlates with negative regulation of the c-myb promoter. Blood 90:1828-39
Skorski, T; Nieborowska-Skorska, M; Wlodarski, P et al. (1997) Treatment of Philadelphia leukemia in severe combined immunodeficient mice by combination of cyclophosphamide and bcr/abl antisense oligodeoxynucleotides. J Natl Cancer Inst 89:124-33
Salomoni, P; Perrotti, D; Martinez, R et al. (1997) Resistance to apoptosis in CTLL-2 cells constitutively expressing c-Myb is associated with induction of BCL-2 expression and Myb-dependent regulation of bcl-2 promoter activity. Proc Natl Acad Sci U S A 94:3296-301

Showing the most recent 10 out of 42 publications