Mutations of the BCR-ABL-kinase domain occur in a minority of patients with stable complete cytogenetic response to imatinib

D. W. Sherbenou, Melissa Wong, A. Humayun, L. S. McGreevey, P. Harrell, R. Yang, M. Mauro, Michael Heinrich, Richard Press, Brian Druker, M. W. Deininger

Research output: Contribution to journalArticle

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Abstract

Residual leukemia is demonstrable by reverse transcriptase-polymerase chain reaction in most patients with chronic myeloid leukemia who obtain a complete cytogenetic response (CCR) to imatinib. In patients who relapse during imatinib therapy, a high rate of mutations in the kinase domain of BCR-ABL have been identified, but the mechanisms underlying disease persistence in patients with a CCR are poorly characterized. To test whether kinase domain mutations are a common mechanism of disease persistence, we studied patients in stable CCR. Mutations were demonstrated in eight of 42 (19%) patients with successful amplification and sequencing of BCR-ABL. Mutation types were those commonly associated with acquired drug resistance. Four patients with mutations had a concomitant rise of BCR-ABL transcript levels, two of whom subsequently relapsed; the remaining four did not have an increase in transcript levels and follow-up samples, when amplifiable, were wild type. BCR-ABL-kinase domain mutations in patients with a stable CCR are infrequent, and their detection does not consistently predict relapse. Alternative mechanisms must be responsible for disease persistence in the majority of patients.

Original languageEnglish (US)
Pages (from-to)489-493
Number of pages5
JournalLeukemia
Volume21
Issue number3
DOIs
StatePublished - Mar 2007

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Cytogenetics
Phosphotransferases
Mutation
Recurrence
Imatinib Mesylate
Mutation Rate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Reverse Transcriptase Polymerase Chain Reaction
Drug Resistance
Leukemia

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Sherbenou, D. W., Wong, M., Humayun, A., McGreevey, L. S., Harrell, P., Yang, R., ... Deininger, M. W. (2007). Mutations of the BCR-ABL-kinase domain occur in a minority of patients with stable complete cytogenetic response to imatinib. Leukemia, 21(3), 489-493. https://doi.org/10.1038/sj.leu.2404554

Mutations of the BCR-ABL-kinase domain occur in a minority of patients with stable complete cytogenetic response to imatinib. / Sherbenou, D. W.; Wong, Melissa; Humayun, A.; McGreevey, L. S.; Harrell, P.; Yang, R.; Mauro, M.; Heinrich, Michael; Press, Richard; Druker, Brian; Deininger, M. W.

In: Leukemia, Vol. 21, No. 3, 03.2007, p. 489-493.

Research output: Contribution to journalArticle

Sherbenou, D. W. ; Wong, Melissa ; Humayun, A. ; McGreevey, L. S. ; Harrell, P. ; Yang, R. ; Mauro, M. ; Heinrich, Michael ; Press, Richard ; Druker, Brian ; Deininger, M. W. / Mutations of the BCR-ABL-kinase domain occur in a minority of patients with stable complete cytogenetic response to imatinib. In: Leukemia. 2007 ; Vol. 21, No. 3. pp. 489-493.
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