The mixed-lineage leukemia (MLL) protein acts as a histone methyltransferase regulating multiple genetic elements. Rearrangements of the MLL gene result in expression of MLL-fusion proteins that occur in some acute leukemias and are associated with poor prognosis. The MLL protein complex has been shown to interact with the androgen receptor via the MLL-menin subunit, thus promoting gene activation. The presence of MLL translocation has not been previously reported in patients with castrate resistant prostate cancer (CRPC). We describe two cases of metastatic CRPC with a translocation in the MLL gene detected by a specific fluorescent in situ hybridization (FISH) assay. Both patients had an aggressive course and succumbed to the illness.
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