DETECTION OF JAK2 MUTATION IN CASES OF MYELODYSPLASTIC SYNDROME

Abstract

Background: JAK2V617F is a tyrosine kinase gain-of-function mutation in exon 14 that results from a guanine-to-thymine transversion at nucleotide 1849 with substitution of valine to phenylalanine at codon 617. The in vitro expression of JAK2V617F results in the constitutive activation of the JAK-STAT pathway and resultant cytokine-independent growth. Aim of the work: Detection of JAK2 mutation in cases of MDS and MDS/MPN to provide practical guidelines, which can allow for a reproducible classification of these types when encountered in clinical practice, and that will benefit of JAK2 inhibitor treatment. Patients and methods: This study comprised 40 newly diagnosed patients divided into two groups: Group I : 20 patients with MDS, Group II: 20 patients with MDS/MPN (2 cases aCML,10 cases CMML,8 cases JMML).All members of this study were subjected to the following :full history taking ,complete clinical examination, routine laboratory investigations including:CBC, stained smear for morphological examination , B.M. aspirate & examination, cytogenetic analysis and detection of JAK2 V617F mutation by Allele Specific PCR technique. Results: In typical forms of MDS JAK2 V617F mutation was very rare (5%) However, a higher percentage of this mutation (55%) was found in patients with MDS/MPN. Positive JAK2 patients with high TLC, LDH may be the main pathology but if negative JAK2 with high TLC, LDH and platelets, we should searched for other mutation that may be in other area of JAK family. Conclusion: our study stated that the presence of JAKV617F mutation may assist in diagnosis of MDS/MPN group than MDS group (odds ratio [OR], 23.2; 95% confidence interval[CI], (2.5-208.6); P=0.001).
Key Words: JAK2 V617F mutation, MDS, MDS/MPN