JAK2 and Beyond: JAK2V617 Mutational Study of Myeloproliferative Disorders and Haematological Malignancies

BACKGROUND: Janus Tyrosine Kinase-2 (JAK2 V617F), a novel point mutation affecting the MPD’S is a somatic gain-of-function mutation. It alters a highly conserved amino acid valine in the negative regulatory JH2 domain to phenylalanine predicted to dysregulate kinase activity. AIM: To evaluate the prevalence and clinical significance of JAK2 V617F mutation in various MPD’s as well as in hematological malignancies. SUBJECTS AND METHODS: JAK2 mutation was assessed in 90 patients with myeloproliferative disorders and 47 leukemic patients. In addition, peripheral blood samples from 90 healthy donors were also collected as control. We used a highly sensitive Allele-Specific polymerase chain reaction (AS-PCR) for the detection and confirmed the mutation further by direct sequencing. RESULTS: Our results showed significant differences between various disorders with respect to either the proportion of positivity or that of mutant alleles. JAK2-V617F was detected in 67/90 MPD patients and 02/17 for AML,01/11 for ALL-L1,02/12 for ALL-L2 and 02/07 for CML and 90 healthy controls. CONCLUSION: From the above findings it is evident that the JAK2 V617F mutation is widespread not only in MPD’s but also in hematological malignancies, which might as well lead to the new classification of MPD’S. Our data also suggest that different genetic events may lead to JAK-STAT pathway activation in different malignancies.