Atypical chronic myeloid leukemia is a clonal hematopoietic disorder characterized by both dysplastic and proliferative features, including persistent granulocytosis with left shift, bone marrow hypercellularity with dysplastic hematopoiesis, and myeloid preponderance; aCML is a disorder of older adults with apparently no sex predominance.1
aCML is a rare myeloid neoplasm with an incidence of 1–2 cases for every 100 cases of Philadelphia-positive CML. Clinical manifestations, similar to those of myeloproliferative syndrom, are related to anemia, thrombocytopenia, and splenomegaly. The etiology and pathogenesis of aCML are not known. The 2016 WHO diagnostic criteria for aCML relies on:
Peripheral blood leukocytosis (WBC ≥ 13 × 109/L) due to increased number of neutrophils and their precursors ≥ 10%.
Dysgranulopoiesis (abnormal chromatin clumbing).
Basophils < 2% of leukocytes, No or minimal absolute basophilia.
Monocytes < 10% of leukocytes, No or minimal absolute monocytosis.
Hypercellular BM with granulocytic proliferation and granulocytic, dysplasia, with or without dysplasia in the erythroid and megakaryocytic lineages.
<20% blasts in the blood and BM.
No Philadelphia chromosome or BCR-ABL fusion gene.
No rearrangement of PDGFRA, PDGFRB, FGFR1 rearrangement or JAK2.
The etiology and pathogenesis of aCML are not known, many gene mutations have been found in aCML, such as, NRAS/KRAS (33% patients), TET2 (33% patients) CBL (10% patients), E2H2 (13% patients) and SETBP1 (25% patients) and so on.5 The syndrome of abnormal chromatin clumping, which has long been recognized as representing a hematologic neoplasm with both myelodysplastic and myeloproliferative features is, in most cases, simply a morphologic variant of aCML; the risk of leukemic transformation is approximately 30%.6 The majority of patients die of BM failure.7
Atypical CML patients showed poor prognosis when treated with conventional chemotherapy, the median survival is only 24 to 25 months.8 A retrospective study in MD Anderson Cancer Center found that: Age (>65 years), anemia (hemoglobin < 10 g/dL), white blood cell count (WBC > 50 × 109/L) are three independent factors in aCML.8, 9
Treatment options such as AML induction type chemotherapy followed by an allogeneic stem cell transplantation are an option for only a minority of patients, but are the only modality that offers a cure.
In aCML is difficult to distinguish from other subtypes of MPS (CML, CNL and CMML), which is easy to misdiagnosis clinically. The presence of a granulocytic proliferation associated with marked dysgranulopoiesis and the absence of BCR-ABL1 translocation are the defining features of aCML.