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Titolo:
CONTRASTING EFFECTS OF RH-MIP-1-ALPHA AND TGF-BETA(1) ON CHRONIC MYELOID-LEUKEMIA PROGENITORS IN-VITRO
Autore:
HOLYOAKE TL; FRESHNEY MG; SPROUL AM; RICHMOND LJ; ALCORN MJ; STEWARD WP; FITZSIMONS E; DUNLOP DJ; FRANKLIN IM; PRAGNELL IB;
Indirizzi:
CRC,BEATSON LABS,GARSCUBE ESTATE,SWITCHBACK RD GLASGOW G61 1BD SCOTLAND GLASGOW ROYAL INFIRM,LRF LABS GLASGOW G4 0SF SCOTLAND WESTERN INFIRM & ASSOCIATED HOSP,DEPT MED ONCOL GLASGOW G11 6NT SCOTLAND MONKLANDS DIST HOSP,DEPT HAEMATOL AIRDRIE SCOTLAND
Titolo Testata:
Stem cells
, volume: 11, anno: 1993, supplemento:, 3
pagine: 122 - 128
SICI:
1066-5099(1993)11:<122:CEORAT>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
STEM-CELL PROLIFERATION; GROWTH-FACTOR; INVIVO;
Keywords:
CHRONIC MYELOID LEUKEMIA; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; TRANSFORMING GROWTH-FACTOR-BETA(1); CFU-A; IN-VITRO CLONOGENIC ASSAY; BCR ABL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
14
Recensione:
Indirizzi per estratti:
Citazione:
T.L. Holyoake et al., "CONTRASTING EFFECTS OF RH-MIP-1-ALPHA AND TGF-BETA(1) ON CHRONIC MYELOID-LEUKEMIA PROGENITORS IN-VITRO", Stem cells, 11, 1993, pp. 122-128

Abstract

In chronic myeloid leukemia (CML) an abnormality at the stem cell level results in unregulated expansion of myeloid progenitors. The mechanism underlying this uncontrolled proliferation remains unclear. An in vitro clonogenic assay which detects the human counterpart of the murine colony forming unit (CFU) CFU-A/CFU-S day 12 was described in a report of our recent findings. CML bone marrow samples were found to proliferate in the CFU-A assay, producing colonies morphologically indistinguishable from normal controls. The bcr/abl transcripts were sought in the RNA from individual colonies using the polymerase chain reaction(PCR). For the five CML samples tested to date, the majority of CFU-Acolonies at diagnosis or in early chronic phase were found to be bcr/abl positive. For normal controls both macrophage inflammatory protein-1alpha (MIP-1alpha) and transforming growth factor-beta1 (TGF-beta1) inhibited the proliferation of CFU-A colonies when directly added to the assay. In contrast, CML progenitors responded normally to TGF-beta1, but showed no response to MIP-1alpha. In suicide assays, for five normal bone marrow samples, CFU-A progenitors induced into S-phase returned to a quiescent state after treatment with MIP-1alpha. CML progenitors demonstrated inherently high cycle status which showed no definiteresponse to MIP-1alpha. However, TGF-beta1 resulted in quiescence of CML progenitor cycling. tn conclusion, the primitive progenitors from CML samples were inhibited normally by TGF-beta1 but showed no response to MIP-1alpha. Therefore, MIP-1alpha should have clinical potential as a protective agent during chemotherapy or for chemotherapeutic purging of CML bone marrow grafts in vitro, allowing selective killing of the malignant population.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/09/20 alle ore 16:57:47