Atypical CML (aCML) is a rare type of myelodysplastic/myeloproliferative neoplasm that resembles chronic myeloid leukemia but lacks the pathognomonic BCR-ABL1 rearrangement and encompasses dysplastic features.

Peripheral blood morphology shows high white cell count >13x109/L with left shift and dysplastic features of neutrophils, such as abnormally clumped chromatin and hypogranularity. Basophilia is absent or minimal. Monocyte count might be increased but it is always less than 10% of the WBC. This is especially important to differentiate it from Chronic myelomonocytic leukemia. Hemoglobin levels and platelet count vary but anemia and thrombocytopenia are not uncommon.

Bone marrow shows hypercellularity due to expanded granulopoiesis. Dysgranulopoiesis is similar to the peripheral blood but multilineage dysplasia could be present as well. Blast percentage may be increased but should be <20%.

In addition to the lack of BCR_ABL1, these neoplasms should not have PDGFRA, PDGFRB, FGFR1 rearrangements or PCM1-JAK2. MPN related abnormalities - JAk2, CALR or MPL - exclude the diagnosis of aCML. SETBP1 and ETNK1 mutations are relatively common in these cases.

Prognosis is poor with median survival of 14-29 months. Up to one third of patients evolve to AML and most of the remaining develop bone marrow failure. Bone marrow transplant may improve the outcome.

This slide shows Bone Marrow biospy, H&E stain. See related content for Bone Marrow biopsy, Reticulin stain, Bone Marrow aspirate (H&E and Iron stains) and Peripheral Blood smear.