Low Incidence of V617FJAK2 Mutation in Acute Myeloid Leukemia and Myelodysplastic Syndromes

Background: V617F JAK2 mutation is a typical molecular finding in BCR-ABL-negative myeloproliferative neoplasms (MPN). The same abnormality has also been reported in other myeloid malignancies. However, the data regarding the incidence and clinical relevance of V617F JAK2 in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are conflicting.

Aim: To establish the incidence and clinical significance of V617F JAK2 mutation in AML and MDS patients in our institution.

Materials and Methods: AML and MDS patients with isolated bone marrow mononuclear cells were included in this study, as follows: (i) 139 AML patients (71 females; 68 males; mean age of 57.5±15.3 years), including: 122 - de novo AML, 7 - therapy related AML (t-AML) and 10 - secondary AML (sAML) after primary MPN [3 V617F JAK2(+), 2 V617F JAK2(-) and 5 with unknown initial V617F JAK2 status]; (ii) 35 MDS patients. V617F JAK2 mutation status was determined using allele-specific polymerase chain reaction (PCR) and PCR RFLP (Restriction Fragment Lenght Polymorphism) analysis.

Results: V617F JAK2 mutation was detected in 3 AML patients: (i) in 1/122 (0.8%) de novo AML patients - male patient with minimally differentiated AML, with no antecedent MPN and the leukemic population showed aberrant myeloid phenotype with co-expression of CD7 and overexpression of EVI1 gene, (ii) in 2/10 (20.0%) patients with sAML after MPN and both patients had V617F JAK2(+) sAML after V617F JAK2(+) primary myelofibrosis. Interestingly; in the same group, a female patient with V617F JAK2(+) essential thrombocythemia developed 5 years later V617F JAK2(-) sAML with an aberrant myelomonocytic phenotype and co-expression of CD56. None of the patients with t-AML or MDS tested positive for V617F JAK2.

Conclusion: V617F JAK2 mutation is a rare finding in AML and MDS patients. Higher incidence was observed in sAML after MPN. However, the mutation status at the AML stage may not be identical as that detected during the primary MPN.