Uncommon phenotypes of BCR::ABL1-positive chronic myelogenous leukemia: a review

Abstract

BCR::ABL1-positive chronic myelogenous leukemia (CML) presents with a typical phenotype in over 95 percent of cases. These are associated with a p210kDa oncoprotein (M-bcr genotype). In these cases, the consideration of CML is high on the differential diagnosis list and appropriate genetic studies to confirm the BCR::ABL1 oncogene are de rigueur. The elevated white cell count, dominant granulocytes, myeloid immaturity and the absent to low blast concentration in the blood, the mild anemia, the normal platelet count or mild thrombocytosis and the frequency of basophilia usually point to the tentative diagnosis of CML or CML is included in the differential diagnosis without ambiguity.

In a very small fraction of cases, the diagnosis of BCR::ABL1-positive CML is less evident. These syndromes include (i) BCR::ABL1-positive thrombocythemia, (ii) so-called neutrophilic BCR::ABL1-positive CML and (iii) the m-bcr (p190BCR-ABL1) variant of CML, often with an absolute and relative monocytosis. In these uncommon forms, there are often misleading blood cell counts. An interesting biological feature is the striking predominance of females in these three atypical presentations. In the fourth variant, (iv) eosinophilic predominant CML, the five reported cases have all been in males. We also consider the very rare phenomenon of (v) smoldering CML (syn. pre-CML or aleukemic CML), which also has a female predominance. The misdiagnosis or delayed diagnosis of these atypical syndromes is consequential because of the beneficial response to tyrosine kinase inhibitors (TKIs) in these patients.