Role of the STAT1 pathway in apoptosis induced by fludarabine and JAK kinase inhibitors in B-cell chronic lymphocytic leukemia

Luis Martinez-Lostao, Javier Briones, Ignasi Forné, Monica Martinez-Gallo, Beatriz Ferrer, Jordi Sierra, Jose Luis Rodriguez-Sanchez, Candido Juarez

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26 Citations (Scopus)

Abstract

Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors that have been implicated in tumoral transformation, especially in hematological malignancies. Because of this, the JAK/STAT pathway is attractive as a therapeutic target in these tumors. In the present study, we analyzed the ability of fludarabine and two JAK kinase inhibitors, AG490 and WHI-P131, to block STAT1 activation and induce apoptosis on B-cell chronic lymphocytic leukemia (B-CLL) cells. All drugs were able to induce a high percentage of apoptosis on B-CLL cells from all patients studied. However, only AG490 and WHI-P131 were able to strongly suppress the STAT1 activation of B-CLL cells. In conclusion, our data show that JAK kinase inhibitors, such as AG490 and WHI-P131 are able to inhibit the STAT1 pathway on B-CLL cells and are strong inductors of apoptosis on these cells. © 2005 Taylor & Francis Group Ltd.
Original languageEnglish
Pages (from-to)435-442
JournalLeukemia and Lymphoma
Volume46
DOIs
Publication statusPublished - 1 Mar 2005

Keywords

  • AG490
  • Apoptosis
  • B-CLL
  • Fludarabine
  • STAT1
  • WHI-P131

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