Prdm16 (1p36) Translocations Define A Distinct Entity Of Myeloid Malignancies With Poor Prognosis But May Also Occur In Lymphoid Malignancies

6531 Background: The PRDM16 gene on chromosome 1p36 is reported to be rearranged in sparse cases of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21). Methods: We report the largest series to date of 39 cases of hematological malignancies with PRDM16 alterations out of a series of 120 cases with 1p36 rearrangements screened by fluorescence in situ hybridization (FISH). Results: PRDM16 was found to be rearranged with the RPN1 locus (3q21) in 30 cases and with other loci in 9 cases. The PRDM16 rearrangements are not restricted to myeloid malignancies, as we characterized two cases of lymphoid proliferation with translocations involving PRDM16. We identified novel translocation partners of PRDM16, including transcription factors ETV6 and IKZF1. This is the first report of a translocation involving IKZF1 in a myeloid malignancy. Translocations involving PRDM16 are original in that they lead to its over-expression through 2 different mechanisms (transcriptional upregulation by promoter switch or formation of a chimeric gene). Survival data interestingly suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis whatever the partner gene, RPN1 versus others. The 32 patients with available survival data had a poor prognosis, as the median overall survival (OS) was 18 months [95% CI, 6 to 31 months] and 5-year OS was 25.7% [95% CI, 8.4-43.0%]. Conclusions: Our study confirms that AML/MDS with PRDM16 translocations share numerous characteristics with AML/MDS associated with translocations involving EVI1 (3q26), which is another transcription factor with a PR domain. If this poor prognosis is confirmed, we propose the addition of a “PRDM16”-entity in the WHO classification of AML/MDS, as is already the case for AML with EVI1 translocations. This new entity could later be broadened to a “PR domain gene rearrangements” subgroup to encompass the AML with EVI1 translocations.