p38 MAP kinase regulates stem cell apoptosis in human hematopoietic failure

Li Zhou, Joanna Opalinska, Amit Verma

Research output: Contribution to journalReview article

39 Scopus citations

Abstract

Myelodysplastic syndromes (MDS) are clonal stem cell disorders that lead to ineffective hematopoiesis and are common causes of low blood counts in the elderly. The exact molecular mechanisms regulating increased stem apoptosis in these disorders are not well defined. p38 MAPK activation is important in regulating the growth inhibitory signals of TNF-α, TGF-β and Interferons on human hematopoiesis. Our findings show that p38 MAPK is overactivated in myelodysplasia bone marrows and regulates hematopoietic stem cell apoptosis. Inhibition of p38 MAPK by genetic or pharmacologic means decreases apoptosis and stimulates in vitro hematopoiesis from primary MDS hematopoietic progenitors. These studies point to the potential efficacy of selective p38α inhibitor, SCIO-469, in human bone marrow failure.

Original languageEnglish (US)
Pages (from-to)534-537
Number of pages4
JournalCell Cycle
Volume6
Issue number5
DOIs
StatePublished - Mar 1 2007

Keywords

  • Apoptosis
  • Bone marrow
  • Hematopoiesis
  • MAP kinase
  • MDS
  • p38

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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