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Titolo:
Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome
Autore:
Letestu, R; Vitrat, N; Masse, A; Le Couedic, JP; Lazar, V; Rameau, P; Wendling, F; Vuillier, J; Boutard, P; Plouvier, E; Plasse, M; Favier, R; Vainchenker, W; Debili, N;
Indirizzi:
Inst Gustave Roussy, INSERM U362, Lab Associe Comite Paris Ligue Natl 5, F-94805 Villejuif, France Inst Gustave Roussy Villejuif France F-94805 , F-94805 Villejuif, France Inst Gustave Roussy, Villejuif, France Inst Gustave Roussy Villejuif France Gustave Roussy, Villejuif, France CHU Jean Minjoz, Hematol Serv, Besancon, France CHU Jean Minjoz BesanconFrance Minjoz, Hematol Serv, Besancon, France CHU Cote Nacre, Hematol Serv, Caen, France CHU Cote Nacre Caen FranceCHU Cote Nacre, Hematol Serv, Caen, France CHU St Jacques, Unite Hematol Infantile, Besancon, France CHU St Jacques Besancon France nite Hematol Infantile, Besancon, France Ctr Hosp Albertville, Serv Pediat, Albertville, France Ctr Hosp Albertville Albertville France erv Pediat, Albertville, France Hop Armand Trousseau, Serv Hematol Biol, Paris, France Hop Armand Trousseau Paris France eau, Serv Hematol Biol, Paris, France
Titolo Testata:
BLOOD
fascicolo: 5, volume: 95, anno: 2000,
pagine: 1633 - 1641
SICI:
0006-4971(20000301)95:5<1633:EOADBA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
DIAMOND-BLACKFAN ANEMIA; C-MPL; THROMBOPOIETIN RECEPTOR; MICE LACKING; BONE-MARROW; DEFECTIVE MEGAKARYOCYTOPOIESIS; CONGENITAL THROMBOCYTOPENIA; HEMATOPOIETIC PROGENITORS; ESSENTIAL THROMBOCYTHEMIA; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Debili, N Inst Gustave Roussy, INSERM U362, Lab Associe Comite Paris LigueNatl 5, F-94805 Villejuif, France Inst Gustave Roussy Villejuif France F-94805 Villejuif, France
Citazione:
R. Letestu et al., "Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome", BLOOD, 95(5), 2000, pp. 1633-1641

Abstract

The thrombocytopenia and absent radii (TAR) syndrome is a rare disease associating bilateral radial agenesis and congenital thrombocytopenia, Here, we investigated in vitro megakaryocyte (MK) differentiation and expression of c-mpl in 6 patients. Using blood or marrow CD34(+) cells, the colony-forming unit (CFU)-MK number was markedly reduced. CD34(+) cells were also cultured in liquid medium in the presence of a combination of 3 cytokines (stemcell factor, interleukin-3, and interleukin-6) or megakaryocyte growth anddevelopment factor (PEG-rHuMGDF) with or without SCF, In the presence of PEG-rHuMGDF, the majority of mature megakaryocytes (CD41 high, CD42 high) underwent apoptosis, This phenomenon was also observed in cultures stimulatedby three cytokines, However, this last combination of cytokines allowed a more complete terminal MK differentiation. Surprisingly, a homogeneous population of CD34(-)CD41(+)CD42(-) cells accumulated during the cultures. Thispopulation was unable to differentiate along the myeloid pathways. This result suggests that a fraction of MK cells is unable to differentiate in theTAR syndrome, We subsequently investigated whether this could be related to an abnormality in c-mpl, No mutation or rearrangement in the c-mpl gene was found by Southern blots or by sequencing of the c-mpl coding region and its promoter in any of the patients. Using Western blot analysis, a decreased level of MpI was found in patient platelets. A decreased level of c-mpl messenger RNA in TAR platelets was also detected with a lower c-mpl-P to c-mpl-K ratio in comparison to adult platelets. Altogether, these results demonstrate that the thrombocytopenia of the TAR syndrome is associated with adysmegakaryocytopoiesis characterized by cells blocked at an early stage of differentiation. (C) 2000 by The American Society of Hematology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 15:32:30