Primary imatinib resistance in chronic myeloid leukemia patients in a developing country: BCR-ABL kinase domain mutations or BCR-ABL independent mechanisms?

Malays J Pathol. 2017 Aug;39(2):107-113.

Abstract

Clinical resistance to imatinib (IM) in chronic myeloid leukemia (CML) carries adverse consequences. We investigated 22 CML patients who developed IM-resistance for BCR-ABL kinase domain (KD) mutations. The median follow-up for this study was 101.9 months (range: 22.2 to 176.5 months) and the estimated mean overall survival was 150.87 months (95% CI: 130.0 to 171.0). Five out of 22 patients tested positive for BCR-ABL KD mutations: 2 had T315I, 2 had E255K and 1 had V289F mutations. Of the remaining 17 patients who did not harbor BCR-ABL KD mutations, 11 patients received nilotinib while the rest continued on IM. All 17 achieved haematological remission but only 5 patients achieved complete cytogenetic remission, 4 of whom did so after switching to nilotinib. Our study shows that most of our IM-resistant patients do not test positive for BCR-ABL KD mutations by available testing methods and the role of second generation tyrosine kinase inhibitors remains undetermined. A critical analysis of the BCR-ABL KD mutations and the underlying mechanisms/ pathways of BCR-ABL independent IM-resistance along with potential treatments in the horizon will be discussed.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Developing Countries
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Humans
  • Imatinib Mesylate / therapeutic use*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Malaysia
  • Male
  • Middle Aged
  • Mutation
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl