Abstract
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 (As2O3) 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.
Highlights
Acute promyelocytic leukaemia (APL) is characterised by the PMLRARA fusion caused by t(15;17)(q22;q12) translocation
APL cases carry gene fusions involving RARG, which is a member of the same retinoid acid receptor (RAR) family and shares high homology (90%) with RARA and RARB
NUP98-RARG, PML-RARG and CPSF6-RARG translocations have been reported in a total of five acute myeloid leukaemia (AML) patients resembling APL.[1,2,3,4]
Summary
Acute promyelocytic leukaemia (APL) is characterised by the PMLRARA fusion caused by t(15;17)(q22;q12) translocation. APL cases carry gene fusions involving RARG, which is a member of the same retinoid acid receptor (RAR) family and shares high homology (90%) with RARA and RARB. In 2011, Such et al reported the first APL case harbouring a rearrangement of RARG.[1] To date, NUP98-RARG, PML-RARG and CPSF6-RARG translocations have been reported in a total of five acute myeloid leukaemia (AML) patients resembling APL.[1,2,3,4] Here, we describe the first case with a novel NPM1-RARG-NPM1 chimeric fusion in an old male with morphological and immunophenotypical features of hypergranular APL but lacking response to all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) therapy
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