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The RARG gene is a member of the nuclear hormone receptor superfamily and shares high homology with RARA and RARB. RARA is involved in translocation with PML in acute promyelocytic leukaemia (APL). Little is known about RARB or RARG rearrangement. RARG fusions were reported in only five APL patients and the partner genes were NUP98, PML and CPSF6. Here, we report NPM1 as a new partner gene of RARG and identify a unique NPM1-RARG-NPM1 chimeric fusion for the first time in an old male with morphological and immunophenotypical features of hypergranular APL but lacking response to all-trans retinoic acid (ATRA) and arsenic trioxide (As 2 O 3 ) therapy. The structural features of the fusion transcript may account for the clinical resistance of the patient. RARG fusion is rare but recurrent in APL, further investigation in larger cohorts is expected to assess frequency, clinical characteristics and outcomes of RARG-translocation in APL.

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Chromosome translocation t(12;22)(p13;q12)/MN1-ETV6 and MN1 overexpression confer a subset of adverse prognostic AML but so far lack in-depth research. We focused on the clinical course and comprehensive genetic analysis of eight cases with t(12;22)(p13;q12) and one with t(12;17;22) (p13;q21;q13) to elucidate their molecular etiology and outcomes of allogeneic hemopoietic stem cell transplantation (allo-HSCT). The total incidence of t(12;22)(p13;q12) and related translocations was 0.32% in myeloid neoplasms. These patients were confirmed to have dismal prognosis when treated only with chemotherapy, and we firstly provided evidence that they can significantly benefit from timely allo-HSCT. Five cases were MN1-ETV6 positive, and a novel MN1-STAT3 fusion was identified in the patient with triadic translocation. Significant MN1 overexpression was observed in all three MN1-fusion-negative cases. Genetic analysis highlighted the evidence of an ectopic super-enhancer associated orchestrated mechanism of MN1 overexpression and ETV6 haploinsufficiency in t(12;22) (p13;q12) myeloid neoplasms, rather than the conventional thought of MN1-ETV6 fusion formation. We also disclosed the high concomitance of trisomy 8 and 531 Kbps focal 8q duplication in t(12;22)(p13;q12) cases. The new perspective about this entity of disease will enlighten further research to define the mechanism of tumorigenesis and discover effective treatments for MN1-driven malignancies.