Atypical chronic myeloid leukemia as defined in the WHO classification is a JAK2 V617F negative neoplasm

Atypical chronic myeloid leukemia (aCML) as defined by the WHO classification is a rare hematopoietic stem cell disorder, which shows both myeloproliferative as well as myelodysplastic features. Because of the presence of neutrophilic leukocytosis, aCML may resemble chronic myelogenous leukemia. However, in contrast with the latter, aCML lacks a Philadelphia chromosome or the BCR/ABL fusion gene. The molecular pathogenesis of aCML and its relationship to other myeloproliferative neoplasms is unknown. To clarify these points, the presence of JAK2 V617F was examined by a retrospective analysis of archival specimens obtained from two large medical institutions. Paraffin-embedded bone marrow (BM) trephines and clot sections were examined by an allele-specific TaqMan PCR suitable for use with decalcified tissue. Fifty-nine cases of Philadelphia (Ph) chromosome negative chronic myeloproliferative neoplasms (CMPN) and normal bone marrows (BM) served as controls. None of the nine amplifiable cases of aCML and none of the normal BM controls showed a JAK2 V617F mutation, in contrast to 45/59 (76%) of the Ph chromosome negative CMPN cases. Atypical CML should therefore be considered as a JAK2 negative chronic myeloid neoplasm that remains properly categorized, alongside chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia, within the WHO group of myelodysplastic/myeloproliferative neoplasms.