Guidez F, Huang W, Tong J H, Dubois C, Balitrand N, Waxman S, Michaux J L, Martiat P, Degos L, Chen Z
Laboratoire de Biologie Cellulaire Hématopoïétique, Institut d'Hématologie, Hôpital Saint Louis, Paris, France.
Leukemia. 1994 Feb;8(2):312-7.
All-trans retinoic acid (ATRA) is a potent inducer of differentiation and cell death in malignant cells. Its effect is known to be mediated through binding to specific nuclear (RARs and RXRs) or cytoplasmic (CRABP) proteins. ATRA is strikingly effective in acute promyelocytic leukemia (the AML3 subtype) inducing a high incidence of complete remissions. Paradoxically, most AML3 cells harbor an abnormal retinoic acid receptor (PML/RAR alpha) resulting from the t(15;17) translocation. Though few AML3 patients do not respond to ATRA therapy, individualization of these cases is of practical importance. Recently the RAR alpha gene has been demonstrated to be involved in a novel fusion transcript (PLZF/RAR alpha) through a t(11;17) translocation. We describe here the second case of such a patient with a t(11;17)-PLZF/RAR alpha leukemic clone. Southern analysis revealed that the breakpoint in the RAR alpha gene was within the second intron (as for PML/RAR alpha) and the intron separating the second and third zinc finger of the PLZF gene. In vitro, the leukemic cells did not show increased NBT reduction or loss of self-renewal after incubation with ATRA. After therapy with ATRA, only partial remission was obtained. These results suggest that the t(11;17) (PLZF/RAR alpha) case of this study was less responsive to ATRA therapy than t(15;17) (PML/RAR alpha) cases and raises the question of the definition of this novel AML subtype.
全反式维甲酸（ATRA）是恶性细胞分化和细胞死亡的有效诱导剂。已知其作用是通过与特定的核蛋白（维甲酸受体RARs和维甲酸X受体RXRs）或细胞质蛋白（细胞视黄酸结合蛋白CRABP）结合来介导的。ATRA在急性早幼粒细胞白血病（AML3亚型）中具有显著疗效，可诱导高比例的完全缓解。矛盾的是，大多数AML3细胞因t(15;17)易位而携带异常的维甲酸受体（PML/RARα）。虽然少数AML3患者对ATRA治疗无反应，但对这些病例进行个体化治疗具有实际意义。最近，RARα基因已被证明通过t(11;17)易位参与一种新的融合转录本（PLZF/RARα）的形成。我们在此描述第二例患有t(11;17)-PLZF/RARα白血病克隆的患者。Southern分析显示，RARα基因的断点位于第二个内含子内（与PML/RARα情况相同）以及分隔PLZF基因第二个和第三个锌指的内含子中。在体外，白血病细胞与ATRA孵育后未显示出NBT还原增加或自我更新能力丧失。接受ATRA治疗后，仅获得部分缓解。这些结果表明，本研究中的t(11;17)（PLZF/RARα）病例对ATRA治疗的反应不如t(15;17)（PML/RARα）病例，并引发了对这种新型AML亚型定义的问题。
