Acquired mutation of the tyrosine kinase JAK2V617F in Egyptian patients with myeloid disorders.

Abstract

Janus Kinase 2 (JAK2) is a member of a family of four Janus Kinases, 2, and 3 and tyrosine kinase 2. Mutated JAK2 (V617F) has the ability to activate downstream signal transducer and activator of transcription (STAT)-mediated transcription in the absence of the ligand erythropoietin. The autoinhibitory activity of JAK2 is disrupted by the presence of the V617F mutation. Somatic mutation in JAK2 (V617F) gene has been reported in myeloid disorders. This study reports the prevalence of JAK2V617F using amplification refractory mutation system (ARMS)-polymerase chain reaction in 246 Egyptian patients with different myeloid disorders and studied the relationship between the JAK2V617F mutation and parameters in peripheral blood. The mutation was detected among 88 patients (35.8%) with different myeloid disorders. JAK2V617F was found among 81.4% of polycythemia vera (PV), 50% of essential thrombocythemia, 46.1% of primary myelofibrosis (PMF), 33.3% of philadelphia (Ph)-negative chronic myeloid leukemia, 33.3% of myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN), and 50% of refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) patients. Hemoglobin and white blood cells were significantly higher in the mutated group of MPN including PV, essential thrombocythemia, and PMF, whereas platelet counts were higher among the mutated PV, PMF, RARS-T, and MDS/MPN group. The identification of JAK2V617F mutations has raised the prospect of developing specific JAK2V617F inhibitors to treat mutated patients.

• Authors: Mona Wagdy Ayad, Dalia Nafea
• Journal: Genetic testing and molecular biomarkers (Genet Test Mol Biomarkers) 2011 Jan-Feb Vol. 15 Issue 1-2 Pg. 17-21 ISSN: 1945-0257 [Electronic] United States
• PMID: 21034166 (Publication Type: Journal Article)

Chemical References

• JAK2 protein, human
• Janus Kinase 2

Topics

• Adolescent
• Adult
• Aged
• Child
• Egypt
• Genotype
• Humans
• Janus Kinase 2 (genetics)
• Middle Aged
• Mutation
• Myeloproliferative Disorders (blood, genetics)