Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Groupe Français de Cytogénétique Hématologique, Groupe de Français d'Hematologie Cellulaire, UK Cancer Cytogenetics Group and BIOMED 1 European Community-Concerted Action "Mole-猫眼课题宝

DOI：

10.1182/blood.v96.4.1297.h8001297_1297_1308

发表时间：

2000-08

期刊：

Blood

影响因子：

20.3

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

D. Grimwade;A. Biondi;M. Mozziconacci;A. Hagemeijer;R. Berger;M. Neat;K. Howe;N. Dastugue;J. Jansen;I. Radford‐Weiss;F. Coco;M. Lessard;J. Hernández;É. Delabesse;D. Head;V. Liso;D. Sainty;G. Flandrin;E. Solomon;F. Birg;M. Lafage-Pochitaloff

急性早幼粒细胞白血病（APL）以t为典型（15;17），产生PML-RAR α融合，并预测对类维甲酸的有益反应。然而，相当大的少数APL病例缺乏典型的t(15;17)，促使欧洲工作组的成立进一步表征这一群体。这些病例被提交给在意大利蒙扎举行的研讨会，并进行了形态学、细胞遗传学和分子检查，产生了60例可评估的患者。在大多数病例中（60例中的42例），分子分析显示PML/RAR α重排是由于插入（42例中的28例）或更复杂的机制，包括3-way和简单的变异易位（42例中的14例）。中期荧光原位杂交（FISH）表明，插入最常导致15q上PML-RAR α融合基因的形成。60例车间患者中有11例发现PLZF/RAR α重排，包括2例缺乏t(11;17)（q23;q21）。在一个核型正常的病例中，FISH分析显示RAR α插入到11q23中，PLZF-RAR α是唯一形成的融合基因。2例患者发现t(5;17)， 1例为弥漫性核NPM染色模式，检测到NPM-RAR α和RAR α -NPM转录本。在另一个具有不平衡的der(5)t(5;17)（q13;q21）和核仁NPM定位模式的基因中，排除了NPM/RAR α重排，FISH显示有一个RAR α等位基因缺失。在剩余的5名研讨会患者中，没有发现RAR α重排的证据，这表明在极少数情况下，其他机制可能介导这种疾病的分化阻断。这项研究强调了结合形态学、细胞遗传学和分子分析对优化APL患者管理和更好地了解疾病发病机制的重要性。(血。2000;96:1297 - 1308)

Acute promyelocytic leukemia (APL) is typified by the t(15;17), generating the PML-RAR alpha fusion and predicting a beneficial response to retinoids. However, a sizeable minority of APL cases lack the classic t(15;17), prompting the establishment of the European Working Party to further characterize this group. Such cases were referred to a workshop held in Monza, Italy and subjected to morphologic, cytogenetic, and molecular review, yielding 60 evaluable patients. In the majority (42 of 60), molecular analyses revealed underlying PML/RAR alpha rearrangements due to insertions (28 of 42) or more complex mechanisms, including 3-way and simple variant translocations (14 of 42). Metaphase fluorescence in situ hybridization (FISH) demonstrated that insertions most commonly led to formation of the PML-RAR alpha fusion gene on 15q. In 11 of 60 workshop patients, PLZF/RAR alpha rearrangements were identified, including 2 patients lacking the t(11;17)(q23;q21). In one case with a normal karyotype, FISH analysis revealed insertion of RAR alpha into 11q23, and PLZF-RAR alpha was the sole fusion gene formed. Two patients were found to have t(5;17), one with a diffuse nuclear NPM staining pattern and with NPM-RAR alpha and RAR alpha-NPM transcripts detected. In the other with an unbalanced der(5)t(5;17)(q13;q21) and a nucleolar NPM localization pattern, an NPM/RAR alpha rearrangement was excluded, and FISH revealed deletion of one RAR alpha allele. In the remaining 5 workshop patients, no evidence was found for a rearrangement of RAR alpha, indicating that in rare instances, alternative mechanisms could mediate the differentiation block that typifies this disease. This study highlights the importance of combining morphologic, cytogenetic, and molecular analyses for optimal management of APL patients and better understanding of the pathogenesis of the disease. (Blood. 2000;96:1297-1308)

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