Clinical and laboratory relevance of JAK2 V617F and BCR-ABL co-existence in Philadelphia positive CML patients

Pak J Pharm Sci. 2021 Nov;34(6(Supplementary)):2289-2295.

Abstract

Chronic Myeloid Leukaemia (CML) is characterized by BCR-ABL1 mutation. A number of research studies have published reports of concomitant JAK2-V617F mutation in BCR-ABL positive Chronic Myeloid Leukaemia. This study aims to investigate the frequency of JAK2-V617F mutation in BCR-ABL positive CML cases. After approval from ethical committee, participants were enrolled in the study. A total of 103 samples from CML patients were analysed for the presence of JAK2-V617F mutation using real-time polymerase chain reaction. Patients were monitored for treatment response using real-time quantitative PCR for BCR-ABL1 mutation. Out of 103 samples analysed, 2 patients tested positive for JAK2-V617F mutation. These two patients when treated with standard Tyrosine Kinase Inhibitors (TKI) therapy achieved molecular response and normalized the haemoglobin and white cell counts. However, one patient has sustained thrombocytosis. JAK2 remained positive throughout the treatment course. We could not follow the second patient till the end of the study. JAK2 mutation in BCR-ABL1 mutated CML appears to be rare. Treatment with TKI does not appear to reduce JAK2 mutation burden despite a decrease in BCR-ABL1 copy numbers.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Child
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Hydroxyurea / therapeutic use
  • Janus Kinase 2 / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Middle Aged
  • Mutation Rate
  • Mutation*
  • Prospective Studies
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • BCR-ABL1 fusion protein, human
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Fusion Proteins, bcr-abl
  • JAK2 protein, human
  • Janus Kinase 2
  • nilotinib
  • Hydroxyurea