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Titolo:
Enforced expression of HOXB7 promotes hematopoietic stem cell proliferation and myeloid-restricted progenitor differentiation
Autore:
Care, A; Valtieri, M; Mattia, G; Meccia, E; Masella, B; Luchetti, L; Felicetti, F; Colombo, MP; Peschle, C;
Indirizzi:
Ist Super Sanita, Dept Hematol & Oncol, I-00161 Rome, Italy Ist Super Sanita Rome Italy I-00161 Hematol & Oncol, I-00161 Rome, Italy Ist Nazl Tumori, I-20133 Milan, Italy Ist Nazl Tumori Milan Italy I-20133 st Nazl Tumori, I-20133 Milan, Italy T Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA USA T Jefferson Univ Philadelphia PA USA mmel Canc Ctr, Philadelphia, PA USA
Titolo Testata:
ONCOGENE
fascicolo: 11, volume: 18, anno: 1999,
pagine: 1993 - 2001
SICI:
0950-9232(19990318)18:11<1993:EEOHPH>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
NATURAL-KILLER LYMPHOCYTES; FIBROBLAST GROWTH-FACTOR; HUMAN PERIPHERAL-BLOOD; HOMEOBOX GENES; FUNCTIONAL-ROLE; LEUKEMIA; OVEREXPRESSION; EXPANSION;
Keywords:
homeobox genes; hematopoietic progenitors; retroviral vector expression;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Care, A Ist Super Sanita, Dept Hematol & Oncol, I-00161 Rome, Italy Ist Super Sanita Rome Italy I-00161 & Oncol, I-00161 Rome, Italy
Citazione:
A. Care et al., "Enforced expression of HOXB7 promotes hematopoietic stem cell proliferation and myeloid-restricted progenitor differentiation", ONCOGENE, 18(11), 1999, pp. 1993-2001

Abstract

Hematopoietic progenitor/stem cells (HPCs/HSCs) purified from human adult peripheral blood (PB) were triggered into cycling, retrovirally transduced with HOXB7 and then functionally assayed in vitro. HPCs were assayed in multi- and unilineage differentiation cultures in either liquid phase or semisolid medium, primitive HPCs in the high proliferative potential colony-forming cell (HPP-CFC) evaluation system and putative HSCs in Dexter type long-term culture (LTC) as LTC initiating cells (LTC-ICs), Control experiments ensured that the exogenous HOXB7 gene was constantly expressed, while the endogenous one was barely or not transcribed. Enforced expression of the genemarkedly modulated the proliferation/differentiation program of the entireHSC/HPC population, Enforced HOXB7 expression exerted a potent stimulatoryeffect on the proliferation of the primitive HPC and putative HSC subsets,assayed as HPP-CFCs and LTC-ICs respectively. While not modifying the total number of HPCs, exogenous HOXB7 induced an increase of the number of granulo-monocytic (GM) HPCs [colony-forming unit GM (CFU-GM) CFU-GM, CFU-C and CFU-M, as evaluated by clonogenic assays] and markedly amplified the progeny of both CFU-G and CFU-M, which showed a sustained proliferation through at least 1-2 months (as evaluated in liquid suspension culture). The prolonged proliferative stimulus induced by HOXB7 transfer into LTC, primitive andGM oriented HPC culture was characterized by persistent proliferation of adiscrete population of blast cells and a large pool of differentiated myeloid precursors. Altogether, these results suggest the hypothesis that the proliferative stimulus exerted by exogenous HOXB7 in primitive and GM-oriented HPCs may represent a preleukemic immortalization step. Consistent with the functional role of HOXB7 in the initial ontogenetic phase, these studiesindicate that ectopic HOXB7 expression in early HPCs and HSCs from adult PB stimulates their self renewal, sustained proliferation and myeloid differentiation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 20:51:02