Licht J D, Chomienne C, Goy A, Chen A, Scott A A, Head D R, Michaux J L, Wu Y, DeBlasio A, Miller W H
Division of Molecular Medicine, Mount Sinai Medical Center, New York, NY 10029.
Blood. 1995 Feb 15;85(4):1083-94.
Analysis of a variant translocation t(11;17) in a case of acute promyelocytic leukemia (APL) led to discovery of a novel zinc finger gene, PLZF, fused to the retinoic acid receptor-alpha (RAR alpha) gene. We reviewed the clinical and molecular features of five additional patients with t(11;17)-associated APL. The clinical course of three patients was characterized by early death and three experienced disseminated intravascular coagulation. Morphologically all of the patients fell in a unusual morphologic spectrum of APL, with features intermediate between M2 and M3 AML. All six patients had PLZF-RAR alpha gene fusion as detected by reverse transcription/polymerase chain reaction assay, Southern blotting, or pulsed-field gel electrophoresis. Five of the six patients failed to achieve complete remission after initial chemotherapy or differentiation therapy with all-trans retinoic acid (ATRA). A sixth patient responded to initial chemotherapy, but on relapse failed to respond to ATRA. When tested in vitro, cultured cells from three of the patients failed to differentiate in response to ATRA. APL associated with t(11;17) and fusion of the PLZF and RAR alpha genes is a discrete clinico-pathologic syndrome with a distinctly worse prognosis than t(15;17) APL.
对一例急性早幼粒细胞白血病（APL）中一种变异易位t(11;17)的分析，导致发现了一个新的锌指基因PLZF，它与维甲酸受体α（RARα）基因融合。我们回顾了另外5例与t(11;17)相关的APL患者的临床和分子特征。3例患者的临床病程特点是早期死亡，3例发生了弥散性血管内凝血。形态学上，所有患者均属于APL的一种不寻常形态学谱系，具有介于M2和M3型急性髓系白血病（AML）之间的特征。通过逆转录/聚合酶链反应分析、Southern印迹或脉冲场凝胶电泳检测，所有6例患者均有PLZF-RARα基因融合。6例患者中有5例在初始化疗或全反式维甲酸（ATRA）分化治疗后未达到完全缓解。第6例患者对初始化疗有反应，但复发时对ATRA无反应。在体外试验时，3例患者的培养细胞对ATRA无分化反应。与t(11;17)及PLZF和RARα基因融合相关的APL是一种独立的临床病理综合征，其预后明显比t(15;17)APL差。
