Division of Pathology & Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, 065201, Langfang, China.
Department of Hematology, The 2nd Affiliated Hospital of Harbin Medical University, 150001, Harbin, China.
Br J Cancer. 2019 May;120(11):1023-1025. doi: 10.1038/s41416-019-0456-z. Epub 2019 Apr 18.
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 (AsO) 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.
RARG 基因是核激素受体超家族的一员，与 RARA 和 RARB 具有高度同源性。RARA 参与急性早幼粒细胞白血病（APL）中与 PML 的易位。关于 RARB 或 RARG 重排知之甚少。仅在 5 例 APL 患者中报道了 RARG 融合，其伙伴基因是 NUP98、PML 和 CPSF6。在这里，我们报道了 NPM1 是 RARG 的一个新伙伴基因，并首次在一名老年男性中鉴定到具有超颗粒 APL 的形态学和免疫表型特征但对全反式维甲酸（ATRA）和三氧化二砷（AsO）治疗无反应的独特的 NPM1-RARG-NPM1 嵌合融合。融合转录本的结构特征可能解释了患者的临床耐药性。RARG 融合在 APL 中罕见但反复发生，预计在更大的队列中进一步研究将评估 APL 中 RARG 易位的频率、临床特征和结果。
