Transformation by Abelson Murine Leukemia Virus

Witte, Owen N.

Abstract

This proposal will investigate the molecular mechanisms used by the abl oncogene in its normal and abnormal growth regulation. Comparison of the structures, regulation, hematopoietic transformation activities, and tyrosine kinase enzymatic properties of the murine cellular, and viral forms of the abl gene as well as the translocation derived form of the abl gene found in Chronic Myelogenous Leukemia cells will be performed. Emphasis will be placed on establishing transformed cell models for murine stem cell populations under the regulation of abl or other oncogenes in concert with improved culture techniques. These studies should aid our understanding of the mechanisms of oncogenesis and hematopoietic development.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Cancer Institute (NCI)
• Type: Research Project (R01)
• Project #: 5R01CA027507-10
• Application #: 3167667
• Study Section: Experimental Virology Study Section (EVR)
• Project Start: 1980-05-01
• Project End: 1991-04-30
• Budget Start: 1989-05-01
• Budget End: 1990-04-30
• Support Year: 10
• Fiscal Year: 1989

Institution

• Name: University of California Los Angeles
• Type: Schools of Arts and Sciences
• DUNS #: 119132785
• City: Los Angeles
• State: CA
• Country: United States
• Zip Code: 90095

Publications

Parham, D M; Kelly, D R; Donnelly, W H et al. (1991) Immunohistochemical and ultrastructural spectrum of hepatic sarcomas of childhood: evidence for a common histogenesis. Mod Pathol 4:648-53

Maru, Y; Witte, O N (1991) The BCR gene encodes a novel serine/threonine kinase activity within a single exon. Cell 67:459-68

Kelliher, M; Knott, A; McLaughlin, J et al. (1991) Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene. Mol Cell Biol 11:4710-6

Kelliher, M A; McLaughlin, J; Witte, O N et al. (1990) Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci U S A 87:6649-53

Ponzetto, C; Wadewitz, A G; Pendergast, A M et al. (1989) P150c-abl is detected in mouse male germ cells by an in vitro kinase assay and is associated with stage-specific phosphoproteins in haploid cells. Oncogene 4:685-90

Daley, G Q; McLaughlin, J; Witte, O N et al. (1987) The CML-specific P210 bcr/abl protein, unlike v-abl, does not transform NIH/3T3 fibroblasts. Science 237:532-5

Konopka, J B; Watanabe, S M; Singer, J W et al. (1985) Cell lines and clinical isolates derived from Ph1-positive chronic myelogenous leukemia patients express c-abl proteins with a common structural alteration. Proc Natl Acad Sci U S A 82:1810-4