Radiation-induced leukemia: Comparative studies in mouse and man
We now have a clear understanding of the mechanism by which radiation-induced (T-cell) leukemia occurs. In irradiated mice (radiation-induced thymic leukemia) and in man (acute lymphoblastic T-cell leukemia, T-ALL) the mechanism of leukemogenesis is surprisingly similar. Expressed in the most elementary terms, T-cell leukemia occurs when T-cell differentiation is inhibited by a mutation, and pre-T cells attempt but fail to differentiate in the thymus. Instead of leaving the thymus for the periphery as functional T-cells they continue to proliferate in the thymus. The proliferating pre- (pro-) T-cells constitute the (early) acute T-cell leukemia (A-TCL). This model for the mechanism of T-cell leukemogenesis accounts for all the properties of both murine and human A-TCL. Important support for the model has recently come from work by Ilan Kirsch and others, who have shown that mutations/deletions in the genes SCL (TAL), SIL, and LCK constitute primary events in the development of T-ALL, by inhibiting differentiation of thymic pre- (pro-) T-cells. This mechanism of T-cell leukemogenesis brings several specific questions into focus: How do early A-TCL cells progress to become potently tumorigenic and poorly treatable Is it feasible to genetically suppress early and/or progressed A-TCL cells What is the mechanism by which the differentiation-inhibited (leukemic) pre-T cells proliferate During the first grant year we have worked on aspects of all three questions.
- Research Organization:
- California Univ., San Diego, CA (United States)
- Sponsoring Organization:
- USDOE; USDOE, Washington, DC (United States)
- DOE Contract Number:
- FG03-91ER61171
- OSTI ID:
- 6053623
- Report Number(s):
- DOE/ER/61171-T1; ON: DE92004436
- Country of Publication:
- United States
- Language:
- English
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CELL DIFFERENTIATION
MUTANTS
LEUKEMIA
RADIOINDUCTION
LEUKEMOGENESIS
BIOLOGICAL PATHWAYS
CELL PROLIFERATION
INHIBITION
LYMPHOCYTES
MAN
MICE
PROGRESS REPORT
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENESIS
CONNECTIVE TISSUE CELLS
DISEASES
DOCUMENT TYPES
IMMUNE SYSTEM DISEASES
LEUKOCYTES
MAMMALS
MATERIALS
NEOPLASMS
PATHOGENESIS
PRIMATES
RODENTS
SOMATIC CELLS
VERTEBRATES
560150* - Radiation Effects on Animals