Phosphorylation levels of BCR-ABL, CrkL, AKT and STAT5 in imatinib-resistant chronic myeloid leukemia cells implicate alternative pathway usage as a survival strategy

Iman Jilani, Hagop Kantarjian, Mercedes Gorre, Jorge Cortes, Oliver Ottmann, Kapil Bhalla, Francis J. Giles, Maher Albitar

Research output: Contribution to journalArticle

Abstract

Ex-vivo studies have suggested that imatinib-resistance in chronic myeloid leukemia (CML) patients occurs despite adequate suppression of BCR-ABL activity. Whether BCR-ABL phosphorylation levels differ between imatinib-sensitive and -resistant patients is not known. We compared the phosphorylation of BCR-ABL in 54 previously untreated CML patients and 62 imatinib-resistant CML patients with progressive disease. Resistant patients had significantly lower levels of BCR-ABL, CrkL and AKT phosphorylation than previously untreated patients, but STAT5 phosphorylation showed no difference. These observations suggest that imatinib- resistance is not necessarily dependent on higher activity in BCR-ABL-dependent pathways, but is likely due to the activation of other pathways.

Original languageEnglish (US)
Pages (from-to)643-649
Number of pages7
JournalLeukemia Research
Volume32
Issue number4
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

Fingerprint

Myeloid Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Phosphorylation
Survival
Imatinib Mesylate

Keywords

  • AKT
  • BCR-ABL
  • Chronic myeloid leukemia
  • CrkL
  • Imatinib
  • Resistance
  • STAT5
  • Survival pathways
  • Tyrosine kinase

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Phosphorylation levels of BCR-ABL, CrkL, AKT and STAT5 in imatinib-resistant chronic myeloid leukemia cells implicate alternative pathway usage as a survival strategy. / Jilani, Iman; Kantarjian, Hagop; Gorre, Mercedes; Cortes, Jorge; Ottmann, Oliver; Bhalla, Kapil; Giles, Francis J.; Albitar, Maher.

In: Leukemia Research, Vol. 32, No. 4, 01.04.2008, p. 643-649.

Research output: Contribution to journalArticle

Jilani, Iman ; Kantarjian, Hagop ; Gorre, Mercedes ; Cortes, Jorge ; Ottmann, Oliver ; Bhalla, Kapil ; Giles, Francis J. ; Albitar, Maher. / Phosphorylation levels of BCR-ABL, CrkL, AKT and STAT5 in imatinib-resistant chronic myeloid leukemia cells implicate alternative pathway usage as a survival strategy. In: Leukemia Research. 2008 ; Vol. 32, No. 4. pp. 643-649.
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AU - Gorre, Mercedes

AU - Cortes, Jorge

AU - Ottmann, Oliver

AU - Bhalla, Kapil

AU - Giles, Francis J.

AU - Albitar, Maher

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