• Coexistence of BCR-ABL and Jak2 mutation in Iranian Patients with Philadelphia Positive CML
  • Mozafar Aznab,1 Alireza Farrokhi,2 Fatemeh Ranjbarnejad,3 Tayebeh Ranjbarnejad,4 Kamran Mansouri,5 Davoud Rezazadeh,6,*
    1. Department of Internal Medicine, Faculty of Medicine, Imam Reza Hospital, Kermanshah University of Medical Sciences
    2. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Iran
    3. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
    4. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
    5. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
    6. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran


  • Introduction: Aberrant activation of the JAK/STAT pathway has been reported in multiple hematologic malignancies and solid tumors. Many reports have shown the presence of V617F somatic mutation of JAK2 gene in all Philadelphia-negative (Ph−) myeloproliferative diseases such as polycythaemia vera (PV) and essential thrombocythaemia (ET) but not in Philadelphia-positive (Ph+) CML. However, some reports indicate that some cases of CML may also present with both Ph+ and JAK2V617F mutations. In a recent study, within one large cohort of CML patients, 2.55 % presented both BCR-ABL rearrangement and JAK2-V617F mutation. As a first driver mutation to be described, JAK2V617F represents a gain of function somatic mutation with a G to T mutation at nucleotide 1849, in exon 14, resulting in the substitution of valine to phenylalanine at codon 617. This mutation causes constitutive tyrosine kinase activation of JH2 by disruption the auto-inhibitory feature of JH2. Therefore, there is constant activation of its downstream effector, signal transducer and activation of transcription3 (STAT3), up regulation of anti-apoptotic protein Bcl-xL 3 and enhanced AKT activity that eventually induces dysregulated clonal expansion of hematopoietic progenitors.
  • Methods: 27 patients with suspected Chronic myeloid (myelogenous) leukaemia (CML) were analyzed for the JAK2 V617F mutation. After cDNA extraction form blood samples, detection of the mutation was done using RT-PCR
  • Results: Of 27 patients, 1 (3.7%) patient was positive for the JAK2 V617F mutation, whereas 26 (96.3%) patients were negative.
  • Conclusion: The frequency of the JAK2 mutation in CML patients in our study is compatible with previous reports. The relationship between the JAK2 mutation and hematological indices can be useful in diagnostic and therapeutic strategies.
  • Keywords: BCR-ABL, Jak2 , CML