The V617F JAK2 mutation is uncommon in cancers and in myeloid malignancies other than the classic myeloproliferative disorders

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Abstract
Sequence analysis was used to determine the JAK2 status of 618 cell lines derived from hematologic (132 lines) and nonhematologic (486 lines representing more than 30 different tumor types) malignancies (Table 1). The V617F mutation was not detected in most of the cell lines but was present in 2 acute myeloid leukemia (AML) lines (HEL and HEL-92.1.7). Micro-satellite analysis demonstrated that these were clonally related. We therefore analyzed 211 primary hematologic malignancies (including 90 AML samples) using allele-specific polymerase chain reaction (PCR)1 to detect the V617F allele. The mutation was present in 5 (5.6%) of the AML samples (Table 1). None of the 5 patients had the FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation, or the t(8;21), inv(16), or t(15;17) rearrangements. All 5 were male (P = .06, Fisher exact test) and significantly older than their unaffected counterparts (median ages at diagnosis were 68 years for V617F-positive patients and 52 years for V617F-negative patients; P = .05, Wilcoxon rank-sum test). None of these V617F-positive patients had a prior history of an overt MPD. Although a prior study did not detect JAK2 mutations in AML patients,5 JAK2 rearrangements occur infrequently in hematologic malignancies. The t(9;12), t(8;9), and t(9;22) translocations present in ALL and atypical chronic myeloid leukemia (CML) each disrupt JAK2, generating the translocation Ets leukemia (TEL)/JAK2, pericentriolar material 1 (PCM1)/JAK2, and breakpoint cluster region (BCR)/JAK2 proteins, respectively.6-8 The kinase activity of the TEL/JAK2 fusion protein is required for its leukemogenic properties,9 consistent with the concept that constitutive JAK2 activity resulting from the V617F mutation contributes to the leukemic phenotype.