Driver gene mutation status has been incorporated into the classification and prognostic assessment of patients with acute myeloid leukemia (AML) and, in some cases, these data are used for treatment decisions.1 JAK2 is a nonreceptor tyrosine kinase that plays a fundamental role in hematopoiesis as a key signaling intermediate.2 The JAK2 V617F mutation is present in >95% of patients with polycythemia vera, and in 50% to 60% of patients with essential thrombocythemia and primary myelofibrosis (MF).3 Bone marrow (BM) specimens from these patients usually show characteristic findings, including atypical megakaryocytic hyperplasia with or without reticulin fibrosis. JAK2 V617F mutation also has been reported in chronic myelomonocytic leukemia (CMML) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with ring sideroblasts and thrombocytosis, with a frequency of 8% to 10% and 60%, respectively.4,5 Therapy with JAK2 inhibitors has improved overall survival and disease-related symptoms, and stabilized or improved BM fibrosis in patients with polycythemia vera and primary MF.6–9
In addition to MPN and MDS/MPN, JAK2 V617F mutation has been reported in de novo AML at a low frequency (<5%; Table 1).10–16 Although a limited number of cases have been studied, de novo AML with JAK2 V617F mutation is more common in patients with erythroid or megakaryoblastic AML,15 tends to be associated with aberrant expression of CD19 and CD56, and to have a diploid karyotype.10,12,17 However, a detailed description of BM morphologic features in JAK2 mutation (mut) AML is not available and the affected molecular pathways and clinical outcomes in patients with de novo AML with JAK2 V617F have not been completely elucidated.5
This study describes the clinical characteristics, pathologic findings, and outcomes of patients with AML with JAK2 V617F mutation. Using systematic mutation profiling of de novo AML cases with JAK2 V617F mutation, we show molecular alterations that provide insights into underlying pathogenesis and offer potential therapeutic targets that might be useful to treat this patient subset.
The authors would like to thank Jill Delsigne from Scientific Publications for the editorial editing, and Sherry Pierce from the Department of Leukemia for providing case information.
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