Imatinib (ST1571) provides only limited selectivity for CML cells and treatment might be complicated by silent BCR-ABL genes

Guanchao Jiang, Fan Yang, Marilyn Li, Karen Weissbecker, Sherrie Price, K. C. Kim, Vincent F. La Russa, Hana Safah, Melanie Ehrlich

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Very promising results have been obtained in clinical trials on chronic-phase chronic myeloid leukemia (CP-CML) patients treated with imatinib mesylate (IM; Gleevec®, STI571), a BCR-ABL tyrosine kinase inhibitor. However, we found that IM caused considerable inhibition of normal hematopoietic progenitor cells upon treating control bone marrow (BM) cultures. In vitro IM treatment gave a decrease in the yield and size of colonies from BM of untreated CP-CML patients that was only two to three times that from the normal samples. Moreover, about 30% of myeloid progenitors (CFU-GM) from CML BM still formed colonies in the presence of IM, most of which had BCR-ABL RNA. About half of these treated colonies also displayed methylation of the internal ABL Pa promoter, a CML-specific epigenetic alteration, which was used in this study as a marker for BCR-ABL translocation-containing cells. However, ∼5-8% of the treated or the untreated CML BM-derived colonies had no detectable BCR-ABL RNA by two or three rounds of RT-PCR despite being positive for the internal standard RNA and displaying hallmarks of CML, either t(9;22)(q34;q11) or ABL Pa methylation. Our results indicate that IM is only partially specific for CML progenitor cells compared to normal hematopoietic progenitor cells and suggest that some CML cells may have a silent BCR-ABL oncogene that could interfere with therapy.

Original languageEnglish (US)
Pages (from-to)103-108
Number of pages6
JournalCancer Biology and Therapy
Volume2
Issue number1
StatePublished - Jan 1 2003

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Keywords

  • BCR-ABL
  • Chronic-phase CML
  • DNA methylation
  • Imatinib
  • RT-PCR
  • STI571

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Jiang, G., Yang, F., Li, M., Weissbecker, K., Price, S., Kim, K. C., La Russa, V. F., Safah, H., & Ehrlich, M. (2003). Imatinib (ST1571) provides only limited selectivity for CML cells and treatment might be complicated by silent BCR-ABL genes. Cancer Biology and Therapy, 2(1), 103-108.