Abstract

The planned studies will be a continuation of ongoing projects that reflect a long interests in normal and abnormal growth regulation in the human hematopoietic system. The specific projects include: 1) Cytogenetic and molecular genetic studies in hematopoietic neoplasia. Long-term chromosome studies of the chronic B cell and T cell neoplasms will be extended, to determine their diagnostic and prognostic value and to provide material for ongoing colloborations, with Dr. Carlo Croce, on specific oncogenes involved in the pathogenesis of these disorders and mechanisms of altered gene regulation. 2) Continuation of related studies on chromosomal abnormalities in adult and childhood nonlymphocytic preleukemia, including hemic disorders associated with atypical chromosomal fragility syndromes. These studies will also extend to the molecular level, investigationg genes critically involved in certain nonlymphocytic preleukemias and leukemias. 3) An Additional group of continuing related studies of growth regulation in normal lymphocytes, focusing on the role of interleukins (IL1, IL2) in the """"""""triggering"""""""" of normal human T cells. Various stimulators and inhibitors of T cell proliferation will be used to investigate further the biological pathways involved and related expression of specific genes and proto-oncogens.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
5R35CA042232-04
Application #
3479291
Study Section
(SRC)
Project Start
1986-05-01
Project End
1993-04-30
Budget Start
1989-06-19
Budget End
1990-04-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Zhang, Qian; Capocasale, Renold J; Fox, Floyd E et al. (2002) Diminished expression of the type II receptor for TGFbeta (TGFbetaRII) in T lymphocytes from patients with Sezary syndrome is not due to mutations in the receptor's poly-A tract: limitations of the standard RT-PCR in cDNA sequence analysis of homopolymeri Arch Immunol Ther Exp (Warsz) 50:421-9
Zaki, M; Douglas, R; Patten, N et al. (2000) Disruption of the IFN-gamma cytokine network in chronic lymphocytic leukemia contributes to resistance of leukemic B cells to apoptosis. Leuk Res 24:611-21
Engels, F H; Koski, G K; Bedrosian, I et al. (1999) Calcium signaling induces acquisition of dendritic cell characteristics in chronic myelogenous leukemia myeloid progenitor cells. Proc Natl Acad Sci U S A 96:10332-7
Edwards, R H; Wasik, M A; Finan, J et al. (1999) Evidence for early hematopoietic progenitor cell involvement in acute promyelocytic leukemia. Am J Clin Pathol 112:819-27
Besa, E C; Kunselman, S; Nowell, P C (1998) A pilot trial of 13-cis-retinoic acid and alpha-tocopherol with recombinant human erythropoietin in myelodysplastic syndrome patients with progressive or transfusion-dependent anemias. The Central Pennsylvania Oncology Group. Leuk Res 22:741-9
Felix, C A; Hosler, M R; Slater, D J et al. (1998) MLL genomic breakpoint distribution within the breakpoint cluster region in de novo leukemia in children. J Pediatr Hematol Oncol 20:299-308
Liang, H; Fairman, J; Claxton, D F et al. (1998) Molecular anatomy of chromosome 7q deletions in myeloid neoplasms: evidence for multiple critical loci. Proc Natl Acad Sci U S A 95:3781-5
Megonigal, M D; Rappaport, E F; Nowell, P C et al. (1998) Potential role for wild-type p53 in leukemias with MLL gene translocations. Oncogene 16:1351-6
Felix, C A; Walker, A H; Lange, B J et al. (1998) Association of CYP3A4 genotype with treatment-related leukemia. Proc Natl Acad Sci U S A 95:13176-81
Douglas, R S; Pletcher Jr, C H; Nowell, P C et al. (1998) Novel approach for simultaneous evaluation of cell phenotype, apoptosis, and cell cycle using multiparameter flow cytometry. Cytometry 32:57-65

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