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

Sze Wei Yap, Nor Rafeah Tumian, Raja Zahratul Azma Raja Sabudin, N. A. Sharifah, Salwati Shuib, Noor Hamidah Hussin, M. H. Elias, Chieh Lee Wong

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)107-113
Number of pages7
JournalMalaysian Journal of Pathology
Volume39
Issue number2
Publication statusPublished - 1 Aug 2017

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Developing Countries
Phosphotransferases
Mutation
Cytogenetics
Protein-Tyrosine Kinases
Imatinib Mesylate
Survival

Keywords

  • BCR-ABL mutations
  • Chronic myeloid leukemia
  • Imatinib
  • Nilotinib

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

Primary imatinib resistance in chronic myeloid leukemia patients in a developing country : BCR-ABL kinase domain mutations or BCR-ABL independent mechanisms? / Yap, Sze Wei; Tumian, Nor Rafeah; Raja Sabudin, Raja Zahratul Azma; Sharifah, N. A.; Shuib, Salwati; Hussin, Noor Hamidah; Elias, M. H.; Wong, Chieh Lee.

In: Malaysian Journal of Pathology, Vol. 39, No. 2, 01.08.2017, p. 107-113.

Research output: Contribution to journalArticle

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