JAK2 V617F mutation presence in hematological malignancies
Purpose: The acquired mutation V617F in the gene JAK2 is an important genetic characteristic of myeloproliferative disorders. It causes the activation of Jak/STAT pathway and consequently aberrant cell growth. This cell signaling pathway is activated in different types of cancer. However, few cases of V617F mutation in non-myeloproliferative hematological malignancies have been described and none in other cancers. In this study we analyzed a sample of consecutive patients with the diagnosis of hematological malignancy to detect the V617F mutation in the JAK2 gene.
Methods: Patients with variety of diagnoses of hematological malignancies were included in the study. Genomic DNA was extracted from fixated cytogenetic cell suspensions which were from bone marrow samples. An allele specific polymerase chain reaction was used to detect the presence of the V617F mutation. Locked nucleic acid nucleotide was incorporated in one primer to obtain sufficient allele specificity of amplification.
Results: A total of 212 patients were included in the study. The V617F mutation was detected in 18 patients; 16 of them had the myeloproliferative disorder out of 43 included patients, whereas in 2 positive patients out of 65 the acute myeloid leukemia was diagnosed. All other cases which included other forms of leukemia, myelodysplastic syndrome, and plasmocytoma as well as several types of non Hodgkin lymphoma were negative for the V617F mutation.
Conclusions: As expected, we observed the V617F mutation mostly in patients with myeloproliferative disorders. The presence of V615F mutation in 2 patients with acute myeloid leukemia is in accordance with reported low frequency in acute myeloid leukemias. The absence of the JAK2 mutation in other hematological malignancies also does not contradict previous reports. Finally, the locked nucleic acid modified nucleotides in PCR primers enable highly specific discrimination of different alleles in polymorphisms of interest with allele specific PCR.