Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon α/ara-C

M. C. Müller, N. Gattermann, T. Lahaye, M. W.N. Deininger, A. Berndt, S. Fruehauf, A. Neubauer, T. Fischer, D. K. Hossfeld, F. Schneller, S. W. Krause, C. Nerl, H. G. Sayer, O. G. Ottmann, C. Waller, W. Aulitzky, P. le Coutre, M. Freund, K. Merx, P. PaschkaH. König, S. Kreil, U. Berger, H. Gschaidmeier, R. Hehlmann, Andreas Hochhaus

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphases (n=803) and qualitative and quantitative RT-PCR from peripheral blood samples (n=1117). Complete cytogenetic response (CCR) was achieved in 60 (imatinib, 87%) vs 10 patients (IFN/Ara-C, 14%) after a median observation time of 24 months. Within the first year after CCR, best median ratio BCR-ABL/ABL was 0.087%, (imatinib, n=48) vs 0.27% (IFN/Ara-C, n=9, P=0.025). BCR-ABL was undetectable in 25 cases by real-time PCR, but in only four patients by nested PCR. Median beat response in patients with relapse after CCR was 0.24% (n=3) as compared to 0.029% in patients with continuous remission (n=52, P=0.029). We conclude that (i) treatment with imatinib in newly diagnosed CML patients is associated with a rapid decrease of BCR-ABL transcript levels; (ii) nested PCR may reveal residual BCR-ABL transcripts in samples that are negative by real-time PCR; (iii) BCR-ABL transcript levels parallel cytogenetic response, and (iv) imatinib is superior to IFN/Ara-C in terms of the speed and degree of molecular responses, but residual disease is rarely eliminated.

Original languageEnglish (US)
Pages (from-to)2392-2400
Number of pages9
JournalLeukemia
Volume17
Issue number12
DOIs
StatePublished - Dec 2003
Externally publishedYes

Keywords

  • BCR-ABL
  • Chronic myelogenous leukemia
  • Imatinib
  • Interferon alpha
  • Quantitative PCR

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Müller, M. C., Gattermann, N., Lahaye, T., Deininger, M. W. N., Berndt, A., Fruehauf, S., Neubauer, A., Fischer, T., Hossfeld, D. K., Schneller, F., Krause, S. W., Nerl, C., Sayer, H. G., Ottmann, O. G., Waller, C., Aulitzky, W., le Coutre, P., Freund, M., Merx, K., ... Hochhaus, A. (2003). Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon α/ara-C. Leukemia, 17(12), 2392-2400. https://doi.org/10.1038/sj.leu.2403157