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Titolo:
TGF beta-induced SMAD2 phosphorylation predicts inhibition of thymidine incorporation in CD34(+) cells from healthy donors, but not from patients with AML after MDS
Autore:
Koschmieder, S; Hofmann, WK; Kunert, J; Wagner, S; Ballas, K; Seipelt, G; Hoelzer, D; Ottmann, OG; Kalina, U;
Indirizzi:
Univ Frankfurt, Div Hematol, Dept Internal Med 3, D-6000 Frankfurt, Germany Univ Frankfurt Frankfurt Germany D-6000 Med 3, D-6000 Frankfurt, Germany
Titolo Testata:
LEUKEMIA
fascicolo: 6, volume: 15, anno: 2001,
pagine: 942 - 949
SICI:
0887-6924(200106)15:6<942:TBSPPI>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-BETA; HEMATOPOIETIC PROGENITOR CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; TRANSFORMING GROWTH-FACTOR-BETA-1; MYELODYSPLASTIC SYNDROMES; BONE-MARROW; TNF-ALPHA; THROMBOPOIETIN; PROTEINS; GENE;
Keywords:
CD34(+) cells; AML after MDS; thrombopoietin; transforming growth factor beta; SMAD2; PD098059;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Kalina, U Univ Frankfurt Hosp, Dept Hematol, Theodor Stern Kai 7, D-60590 Frankfurt,Germany Univ Frankfurt Hosp Theodor Stern Kai 7 Frankfurt Germany D-60590
Citazione:
S. Koschmieder et al., "TGF beta-induced SMAD2 phosphorylation predicts inhibition of thymidine incorporation in CD34(+) cells from healthy donors, but not from patients with AML after MDS", LEUKEMIA, 15(6), 2001, pp. 942-949

Abstract

Cells from patients with MDS-derived AML display heterogeneous proliferative responses to transforming growth factor beta (TGF beta). We analyzed growth inhibition and SMAD2 phosphorylation by TGF beta in CD34(+) cells from nine patients, as compared to normal controls. While TGF beta consistently inhibited thymidine incorporation of normal cells (41% of control, P < 0.05), cells from patients with AML were growth-inhibited in only four of sevencases (40%), whereas TGF beta stimulated thymidine incorporation in the three other samples (166%). Remarkably, TPO reverted the stimulatory effect of TGF beta to profound growth inhibition. Upon exposure to TGF beta, SMAD2 protein was phosphorylated in normal CD34(+) cells (n = 3), CD34(+) leukemic blasts from all examined patients with AML (n = 4), and in the myeloid leukemic cell lines M-07e and HEL. TGF beta inhibited TPO-mediated thymidine incorporation, cell proliferation and survival in all samples analyzed. In M-07e cells and CD34(+) cells from healthy donors, this inhibition was enhanced by an antagonist of JAK2 (AG490), but not a MEK-1 antagonist (PD098059). Conversely, in CD34(+) cells from a patient with AML, both AG490 and PD098059 significantly enhanced TGF beta -mediated suppression of TPO-induced thymidine incorporation. Thus, in MDS-derived AML, altered responses to TGFbeta may be due to defects downstream of SMAD2 and may involve MAPK activation.

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Documento generato il 04/04/20 alle ore 14:58:49