Type B Core Binding Factor β/Smooth Muscle Myosin Heavy Chain Fusion Transcript in Myeloid Blast Phase of Chronic Myeloid Leukemia: Correlation with Nuclear and Cytoplasmic Localization of the Fusion Protein

BackgroundInv(16)(p13q22) or the rare t(16;16)(p13;q22) is characteristic of the M4Eo type of acute myeloid leukemia and results in the fusion of the core binding factor β gene (CBFB) at 16q22 with the smooth muscle myosin heavy chain gene (MYH11) at 16p13. The fusion transcript CBFB/MYH11 plays an important role in leukemogenesis. Many variations of this fusion transcript have been reported, with type A being most common and occurring in > 85% of cases.Patients and MethodsWe studied the fusion transcripts in 4 cases of chronic myelogenous leukemia in myeloid blast phase with inv(16)(p13q22).ResultsSequencing analysis revealed type B fusion transcript in 3 of the 4 cases. Immunohistochemistry demonstrated both nuclear and cytoplasmic staining for the fusion protein.ConclusionAlthough the biologic significance of this finding is unknown, the high frequency of an unusual type of fusion transcript in the chronic myelogenous leukemia cases in blast phase in which inv(16)(p13q22) first occurred at the time of blast transformation suggests that the type B transcript might play a role in disease progression. The effect of the additional smooth muscle myosin heavy chain sequences in the type B fusion on subcellular localization of the protein product is also suggested.