BCR-ABL + acute myeloid leukemia: are we always dealing with a high-risk disease?

BCR-ABL 1 acute myeloid leukemia (AML) has recently been listed in the 2016 revised World Health Organization (WHO) classification of myeloid malignancies as a provisional entity. 1 BCR-ABL 1 AML comprises a group of de novo AML in patients without evidence of an underlying chronic myeloid leukemia (CML) and without cooccurring aberrations such as CEBPA, NPM1, inv( Although there is some overlap between BCR-ABL 1 AML, myeloid CML blast crisis, and BCR-ABL 1 mixed phenotype acute leukemia, no definite criteria have yet been defined to distinguish among these entities. However, a loss of IKZF1 and CDKN2A as well as cryptic deletions in IGH and TRG genes have recently been reported in BCR-ABL 1 AML and seem to be absent in myeloid blast crisis of CML. Therefore, these additional molecular markers may be helpful for differential diagnosis in clinically difficult situations. Remarkably, neither guidelines explicitly comment on BCR-ABL 1 AML cases in which BCR-ABL cooccurs with otherwise favorable molecular/cytogenetic markers such as CEBPA, NPM1, and inv(16) (these would exclude a diagnosis as BCR-ABL 1 AML sensu stricto according to WHO 2016) or without additional adverse molecular/cytogenetic features. Considering recent data on the prognosis of BCR-ABL 1 AML, we believe that a general classification as high-risk AML according to ELN might not be appropriate. Given the paucity of clinical cases and the lack of robust data sets on survival and treatment responses, we have recently analyzed all published cases of BCR-ABL 1 AML since 1975. To avoid inclusion of CML blast crisis as far as possible, we excluded cases that, because of the reported clinical features or insufficient information provided, might in fact represent CML blast crisis than de novo AML. Nevertheless, its results regarding the prognosis of BCR-ABL 1 AML are also limited by its retrospective nature, which comprises a period that includes the pre-tyrosine-kinase inhibitor (TKI) era and the lack of data concerning recently reported molecular markers such as IKZF1, CDKN2A, and deletions in IGH or TRG 2 that may help to distinguish between de novo BCR-ABL 1 AML and myeloid blast crisis of CML.