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

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

Fingerprint

Bone Marrow
Leukemia, Myeloid, Chronic Phase
RNA
Hematopoietic Stem Cells
Methylation
Genes
Granulocyte-Macrophage Progenitor Cells
Therapeutics
Oncogenes
Epigenomics
Protein-Tyrosine Kinases
Stem Cells
Clinical Trials
Polymerase Chain Reaction
Imatinib Mesylate

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., ... 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.

Imatinib (ST1571) provides only limited selectivity for CML cells and treatment might be complicated by silent BCR-ABL genes. / Jiang, Guanchao; Yang, Fan; Li, Marilyn; Weissbecker, Karen; Price, Sherrie; Kim, K. C.; La Russa, Vincent F.; Safah, Hana; Ehrlich, Melanie.

In: Cancer Biology and Therapy, Vol. 2, No. 1, 01.01.2003, p. 103-108.

Research output: Contribution to journalArticle

Jiang, G, Yang, F, Li, M, Weissbecker, K, Price, S, Kim, KC, La Russa, VF, 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, vol. 2, no. 1, pp. 103-108.
Jiang, Guanchao ; Yang, Fan ; Li, Marilyn ; Weissbecker, Karen ; Price, Sherrie ; Kim, K. C. ; La Russa, Vincent F. ; Safah, Hana ; Ehrlich, Melanie. / Imatinib (ST1571) provides only limited selectivity for CML cells and treatment might be complicated by silent BCR-ABL genes. In: Cancer Biology and Therapy. 2003 ; Vol. 2, No. 1. pp. 103-108.
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