Unfavorable disease progression in patients with chronic myeloid leukemia and concurrent t(6;9) translocation (DEK::NUP214 fusion) or inversion 16 (CBFB::MYH11 fusion)

The occurrence of additional specific chromosomal abnormalities in Philadelphia chromosome-positive (pH+) cells is associated with disease progression in chronic myeloid leukemia (CML), and is considered a marker that defines the accelerated/blast phase of CML. Both DEK::NUP214 fusion and CBFB rearrangement are extremely rare in CML, and their prognostic significance is unknown. Here we present two CML cases, with one case having concurrent translocation 6;9 [t(6;9)] leading to DEK::NUP214 fusion, and the other one presenting with concurrent inversion 16 -inv(16)- leading to CBFB::MYH11 fusion. The t(6;9) is usually associated with poor prognosis in acute myeloid leukemia (AML) patients. In this case, the patient failed to achieve remission and expired. This suggests that the t(6;9) is also associated with poor prognosis in CML. However, more data is needed to verify this association. Detection of inv(16) by karyotyping is technically challenging. In addition, FISH for CBFB is not usually run in the context of CML, thus raising the possibility that similar cases may have been underdiagnosed. With the routine use of next-generation sequencing (NGS) for gene fusion detection, more patients like this one should be diagnosed and treated accordingly. These cases illustrate the importance of a comprehensive molecular/cytogenetic diagnostic work-up.