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Titolo:
Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia
Autore:
Holyoake, T; Jiang, XY; Eaves, C; Eaves, A;
Indirizzi:
British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada British Columbia Canc Agcy Vancouver BC Canada V5Z 1L3 BC V5Z 1L3, Canada
Titolo Testata:
BLOOD
fascicolo: 6, volume: 94, anno: 1999,
pagine: 2056 - 2064
SICI:
0006-4971(19990915)94:6<2056:IOAHQS>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHRONIC MYELOGENOUS LEUKEMIA; HUMAN HEMATOPOIETIC-CELLS; LONG-TERM-CULTURE; COLONY-STIMULATING FACTOR; IMMUNE-DEFICIENT MICE; BONE-MARROW CELLS; HUMAN CORD-BLOOD; CD34(+) CELLS; IN-VITRO; BCR-ABL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Eaves, A British Columbia Canc Agcy, Terry Fox Lab, 601 W 10th Ave, Vancouver, BC V5Z 1L3, Canada British Columbia Canc Agcy 601 W 10th Ave VancouverBC Canada V5Z 1L3
Citazione:
T. Holyoake et al., "Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia", BLOOD, 94(6), 1999, pp. 2056-2064

Abstract

Chronic myeloid leukemia (CML) is characterized by an increased proliferative activity of the leukemic progenitors that produce an elevated number ofmature granulocytes. Nevertheless, cell cycle-active agents, even in very high doses, are alone unable to eradicate the leukemic clone, suggesting the presence of a rare subset of quiescent leukemic stem cells. To isolate such cells, we first used Hoechst 33342 and Pyronin Y staining to obtain viable G(0) and G(1)/S/G(2)/M fractions of CD34(+) cells by fluorescence-activated cell sorting (FACS) from 6 chronic-phase CML patients' samples and confirmed the quiescent and cycling status of the 2 fractions by demonstration of expected patterns of Ki-67 and D cyclin expression. Leukemic (Ph+/BCR-ABL(+)) cells with in vitro progenitor activity and capable of engrafting immunodeficient mice were identified in the directly isolated Go cells. Single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that many leukemic CD34(+) G(0) cells also expressed BCR-ABL mRNA, CD34(+) from 8 CML patients were also labeled with carboxyfluorescein diacetatesuccinimidyl diester (CFSE) before being cultured (with and without added growth factors) to allow viable cells that had remained quiescent tie, CFSE) after 4 days to be retrieved by FAGS, Leukemic progenitors were again detected in all quiescent populations isolated by this second strategy, including those exposed to a combination of flt3-ligand, Steel factor, interleukin-3, interleukin-6, and granulocyte colony-stimulating factor, These findings provide the first direct and definitive evidence of a deeply but reversibly quiescent subpopulation of leukemic cells in patients with CML with both in vitro and in vivo stem cell properties. (C) 1999 by The American Society of Hematology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 20:04:23