Activity of the BH3 mimetic ABT-737 on polycythemia vera erythroid precursor cells

Ruggero De Maria Marchiano, Federica Francescangeli, Ann Zeuner, Francesca Pedini, Michele Signore, Gabriella Girelli, Agostino Tafuri

Risultato della ricerca: Contributo in rivistaArticolo in rivista

14 Citazioni (Scopus)

Abstract

An increased expression of antiapoptotic molecules is often found in malignant cells, where it contributes to their clonal expansion by conferring an improved survival ability. We found that erythroid precurors derived from patients with polycythemia vera (PV) with medium and high JAK2V617F mutation rates often express elevated levels of the antiapoptotic molecules Bcl-2 and Bcl-XL (5 of 12 patients with 3 to 7 times Bcl-2 and 3 of 12 patients with 4 to 7 times Bcl-XL than average normal controls) and are more resistant to myelosuppressive drugs than normal erythroblasts. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-XL, and Bcl-W, induced apoptosis preferentially in JAK2V617F-high PV erythroid precursors as compared with JAK2V617F-low or normal erythroblasts. ABT-737 inhibited also the proliferation of PV erythroblasts and interfered with the formation of endogenous erythroid colonies by PV hematopoietic progenitors. Altogether, these results suggest that small-molecule inhibitors of Bcl-2/Bcl-XL may be used in the treatment of patients with PV with high JAK2V617F allele burden. © 2009 by The American Society of Hematoloty.
Lingua originaleEnglish
pagine (da-a)1522-1525
Numero di pagine4
RivistaBlood
Volume113
DOI
Stato di pubblicazionePubblicato - 2009

Keywords

  • Apoptosis
  • Biochemistry
  • Biphenyl Compounds
  • Cell Biology
  • Cell Division
  • Cells, Cultured
  • Erythroid Precursor Cells
  • Erythropoiesis
  • Gene Expression
  • Hematology
  • Humans
  • Immunology
  • Molecular Mimicry
  • Nitrophenols
  • Piperazines
  • Polycythemia Vera
  • Proto-Oncogene Proteins c-bcl-2
  • Sulfonamides
  • bcl-X Protein

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