Corey S J, Locker J, Oliveri D R, Shekhter-Levin S, Redner R L, Penchansky L, Gollin S M
Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, PA 15213.
Leukemia. 1994 Aug;8(8):1350-3.
Acute promyelocytic leukemia (APML) almost always involves a chromosomal translocation t(15:17) that results in the fusion of the retinoic acid receptor alpha (RAR alpha) gene with a transcription factor gene called PML. Several cases of APML with t(11;17) have recently been described, involving fusion of the RAR alpha gene with a new zinc finger gene named PLZF. We report here a second non-classical translocation, t(5;17), with a rearranged RAR alpha gene in a child with APML. Based on restriction endonuclease analysis, the rearrangement of RAR alpha occurred within the second intron, the common breakpoint site for t(15;17). The leukemic cells in the bone marrow aspirate were a mixture of hypergranular and hypogranular bilobed promyelocytes. Although less than 1% abnormal promyelocytes were identified after induction therapy, cytogenetics revealed persistent t(5;17). Therefore, the child was treated with all-trans-retinoic acid (ATRA). There was no disease progression, and one marrow was interpreted as remission, with confirmation by cytogenetics which failed to reveal the translocation. However, disease reoccurred shortly after completion of ATRA. This poor response to ATRA may be an additional characteristic associated with non-classical translocations in APML. The identification of a second variant translocation involving the RAR alpha gene in APML suggests yet another RAR alpha rearrangement related to neoplastic myelopoiesis.
急性早幼粒细胞白血病（APML）几乎总是涉及一种染色体易位t(15;17)，该易位导致维甲酸受体α（RARα）基因与一个名为PML的转录因子基因融合。最近已描述了几例伴有t(11;17)的APML病例，涉及RARα基因与一个名为PLZF的新锌指基因融合。我们在此报告一名患APML儿童中的第二种非经典易位t(5;17)，其RARα基因发生重排。基于限制性内切酶分析，RARα的重排发生在第二个内含子内，这是t(15;17)的常见断点位点。骨髓穿刺液中的白血病细胞是高颗粒和低颗粒双叶早幼粒细胞的混合物。尽管诱导治疗后鉴定出的异常早幼粒细胞不到1%，但细胞遗传学显示t(5;17)持续存在。因此，该儿童接受了全反式维甲酸（ATRA）治疗。没有疾病进展，一次骨髓检查被判定为缓解，细胞遗传学确认未发现易位。然而，ATRA治疗完成后不久疾病复发。对ATRA的这种不良反应可能是与APML中非经典易位相关的另一个特征。在APML中鉴定出涉及RARα基因的第二种变异易位提示了另一种与肿瘤性骨髓生成相关的RARα重排。
