Abstract
Background and Objective: Co-existence of myeloproliferative disorders (MPD) and Janus associated kinase 2 mutation (JAK2 V617F) is a well-established fact. Only few case reports are available showing presence of JAK2 V617F mutation in chronic myeloid leukemia (CML). Purpose of this study was to determine the frequency of JAK2 V617F mutation in Philadelphia Chromosome positive (Ph +) CML patients in Pakistan. Methods: The study was conducted from August 2009 to July 2010 at Civil Hospital and Baqai Institute of Hematology (BIH) Karachi. Blood samples from 25 patients with CML were collected. Multiplex reverse transcription polymerase chain reaction (RT-PCR) was performed for Breakpoint Cluster Region – Abelson (BCR-ABL) rearrangement. Conventional PCR was performed for JAK2 V617F mutation on BCR-ABL positive samples. Results: All 25 samples showed BCR-ABL rearrangement. Out of these 11 samples (44%) had JAK2 V617F mutation; the remaining 14 (56%) cases showed JAK2 617V wild type. Conclusion: It is concluded that the co-existence of Ph +CML and JAK2 V617F mutation is possible.
Highlights
The pathognomonic marker of chronic myeloid leukemia (CML) is Ph chromosome that results from a reciprocal chromosomal translocation between the ABL gene1
Chronic Myeloid Leukemia leukocyte count with complete left shift
All 25 samples were positive for Breakpoint Cluster Region – Abelson (BCR-ABL) rearrangements
Summary
JAK2 belongs to the family of intracellular non-receptor TYK It has seven Janus homology (JH) domains (JH1-JH7).[3] JH1 is an elevated tyrosine kinase domain whereas JH2 is an inactive pseudokinase domain. JH2 has auto inhibitory properties any alteration leads to constitutive tyrosine phosphorylation.[4,5] Guanine is present on both loci (G/G) at codon 617 of JAK2.6 There are three types of JAK2 V617F mutation. JAK2 V617F is a gain of function mutation It disrupts the auto-inhibitory property of JH2 leading to constitutive tyrosine kinase activation of JH1.12 There is constant activation of signal transducer and activation of transcription[3] (STAT3), up regulation of anti-apoptotic protein Bcl-xL3 and enhanced AKT activity.[4] This deregulated signaling induces clonal expansion of haematopoietic progenitors that are independent of normal growth factor control.[11]
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