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Titolo:
THE BIOLOGY OF NORMAL AND NEOPLASTIC STEM-CELLS IN CML
Autore:
EAVES C; UDOMSAKDI C; CASHMAN J; BARNETT M; EAVES A;
Indirizzi:
BC CANC RES CTR,TERRY FOX LAB,601 W 10TH AVE VANCOUVER V5Z 1L3 BC CANADA
Titolo Testata:
Leukemia & lymphoma
, volume: 11, anno: 1993, supplemento:, 1
pagine: 245 - 253
SICI:
1042-8194(1993)11:<245:TBONAN>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Keywords:
STEM CELLS; CML; HEMATOPOIESIS; INHIBITORS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
NO
Recensione:
Indirizzi per estratti:
Citazione:
C. Eaves et al., "THE BIOLOGY OF NORMAL AND NEOPLASTIC STEM-CELLS IN CML", Leukemia & lymphoma, 11, 1993, pp. 245-253

Abstract

Chronic myeloid leukemia (CML) has long served as a prototype malignancy for basic as well as clinical studies aimed at developing curativecancer treatment protocols. Well established features of chronic phase CML are its origin in a pluripotent stem cell, a now well defined molecular genetic basis involving the creation of a BCR-ABL fusion gene and evidence of resultant abnormalities in the mechanisms that normally control primitive hemopoietic cell proliferation. We have recently shown how the long-term marrow culture system can be adapted to quantitate and characterize a very primitive cell type in normal blood and marrow samples, as well as their normal and leukemic counterparts in patients with CML. This system has also been used to dissect mechanisms of normal progenitor regulation and to identify specific anomalies affecting leukemic (CML) progenitors. Our studies show that cells detectedby their ability to initiate long-term cultures (LTC) of leukemic cells (i.e., CML LTC-initiating cells or LTC-IC) are differently distributed between marrow and blood by comparison to LTC-IC in normal individuals and. although functionally similar in terms of the number and differentiation types of clonogenic cells they produce, CML LTC-IC exhibit defective self-maintenance. Phenotypically these primitive leukemic cells are heterogeneous; the majority display features of activated/proliferating cells but a significant proportion do not. We have also documented heterogeneity in primitive CML cell responses to two factors that specifically and reversibly arrest the cycling of primitive normal hemopoietic cells. i.e.. TGF-beta and MIP-1alpha, to which CML cellsare normally responsive and abnormally unresponsive, respectively. Taken together, these findings suggest a model of clonal amplification in chronic phase CML based on reduced leukemic stem cell self-renewal potential coupled to partial autonomy from normal growth control mechanisms. In addition. the availability of methods for quantitating and differentially manipulating very primitive leukemic and normal cells from patients with CML should allow the design of more rational and effective treatment protocols.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/02/20 alle ore 17:21:16