Atypical Chronic Myeloid Leukemia, BCR/ABL1 Negative

  • Katherine Boothe Levinson
  • Adam BaggEmail author
Part of the Molecular Pathology Library book series (MPLB, volume 12)


Atypical chronic myeloid leukemia (aCML) is a rare neoplasm of hematopoietic stem cells characterized by overlapping myelodysplastic and myeloproliferative features, whose diagnostic hallmark is an overabundance of dysplastic mature granulocytic cells and their immature precursors in the peripheral blood and bone marrow. For a long time, aCML had no known molecular markers, and was characterized only by the genetic features it lacked, including the defining BCR-ABL1 fusion transcript seen in the superficially morphologically similar chronic myeloid leukemia (CML). Furthermore, some classical non-CML myeloproliferative neoplasms (MPNs), including post-polycythemic/post-essential thrombocythemic myelofibrosis, accelerated-phase MPNs, and chronic neutrophilic leukemia (CNL), may mimic the clinical and laboratory features of aCML. An explosion of genetic research has identified recurrent mutations in SETBP1 and/or ETNK1 in up to one third of patients with aCML. Mutations in these genes not only shed light on possible mechanisms of aCML oncogenesis, but are also relatively specific for aCML, making them potentially useful confirmatory markers. As such, the 2016 revision to the WHO classification of hematopoietic neoplasms indicates that a diagnosis of aCML is supported by the presence of SETBP1 and/or ETNK1 mutations. CSF3R mutations, once thought to be frequent in aCML, are now considered uncommon, occurring in fewer than 10% of cases. If detected, a CSF3R mutation should prompt consideration of alternative diagnoses, particularly CNL. Patients with aCML have also been found to harbor mutations in numerous other genes that are not unique to aCML, but rather, are commonly mutated across the broad spectrum of myeloid neoplasms. Although these mutations have little specific diagnostic utility, they may shed light on the pathogenesis of aCML and could carry increasing significance with the development of novel, targeted therapies. At present, therapeutic options for patients with aCML are limited, and the disease carries a poor prognosis. Although our limited understanding of aCML has improved drastically in recent years, much more research is needed to understand its molecular underpinnings and to improve patient outcomes.


Atypical chronic myeloid leukemia (aCML) BCR-ABL1 negative Myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) SETBP1 ETNK1 CSF3R 


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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineHospital of the University of PennsylvaniaPhiladelphiaUSA

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