Merlat A, Lai J L, Sterkers Y, Demory J L, Bauters F, Preudhomme C, Fenaux P
Service des Maladies du Sang, CHU Lille, France.
Leukemia. 1999 Feb;13(2):250-7. doi: 10.1038/sj.leu.2401298.
Two main types of therapy-related acute myeloid leukemias (tAML) and myelodysplastic syndromes (tMDS) have been described. The first classical type typically occurs late after use of alkylating agents and presents as MDS with -7/del 7q and/or -5/del5q. The second form occurs early after the use of agents targeted at topoisomerase II, and presents as AML with 11q23 or other rearrangements of de novo AML. Recently, we and others reported, in AML and MDS, a strong correlation between cytogenetic rearrangements leading to 17p deletion, a specific type of dysgranulopoiesis and p53 mutation; several of those cases of 17p- syndrome were therapy-related. Over the last 15 years, we observed 25 cases of tAML and tMDS with 17p deletion, which represented 36% of the AML and MDS with 17p deletion diagnosed during that period. Median age was 59 years. Twenty-one patients had tMDS and four tAML. Typical dysgranulopoiesis and p53 mutation and/or overexpression were seen in 22 of 24 and 16 of 19 evaluable patients, respectively. 17p deletion resulted from unbalanced translocations involving 17p (18 cases), monosomy 17 (five cases), i(17q) (one case) or del 17p (one case). Twenty-one patients also had -5/del 5q, and/or -7/del 7q. Median interval from treatment of the first tumor of tAML and tMDS was 94 months (range 19-252). Median survival was only 7 months. Based on primary tumor and antineoplastic agents used, patients could be relatively well divided into two groups: a first group of 11 cases, occurring mainly after a lymphoid neoplasm (eight cases) treated by chemotherapy with an alkylating agent (10 cases), and a second group of 14 cases occurring after essential thrombocythemia (ET) or polycythemia vera (PV) treated mainly by hydroxyurea (10 cases), pipobroman (eight cases), 32P (six cases) but rarely by alkylating agents (two cases). -7/del 7q was found in 10 of the 11 patients in the first group, as compared to three of the 14 patients of the second group (P = 0.0001). Therefore, therapy-related cases represent a high proportion of AML and MDS with the 17p- syndrome. They have many features in common with classical tMDS and tAML, including long interval from the first tumor, a usual preleukemic phase, and frequent occurrence of -5/del 5q. About one half of them, in addition, occur after alkylating agents and generally carry -7/del 7q. The other half, however, occur mainly after ET or PV treated by hydroxyurea or other non-alkylating agents, and usually have no -7/del 7q. These findings bring further support to a possible relationship between prior drugs used and cytogenetic rearrangements in tAML and tMDS.
已描述了两种主要类型的治疗相关急性髓系白血病（tAML）和骨髓增生异常综合征（tMDS）。第一种经典类型通常在使用烷化剂后较晚发生，表现为伴有-7/del 7q和/或-5/del5q的MDS。第二种类型在使用靶向拓扑异构酶II的药物后较早发生，表现为伴有11q23或其他新发AML重排的AML。最近，我们和其他人报道，在AML和MDS中，导致17p缺失的细胞遗传学重排、一种特定类型的粒细胞生成异常和p53突变之间存在很强的相关性；其中一些17p-综合征病例与治疗相关。在过去15年中，我们观察到25例伴有17p缺失的tAML和tMDS，占该时期诊断的伴有17p缺失的AML和MDS的36%。中位年龄为59岁。21例患者患有tMDS，4例患有tAML。在24例可评估患者中的22例以及19例可评估患者中的16例中分别观察到典型的粒细胞生成异常和p53突变及/或过表达。17p缺失是由涉及17p的不平衡易位（18例）、17号染色体单体（5例）、i(17q)（1例）或del 17p（1例）导致的。21例患者还伴有-5/del 5q和/或-7/del 7q。tAML和tMDS首例肿瘤治疗后的中位间隔时间为94个月（范围19 - 252个月）。中位生存期仅7个月。根据原发肿瘤和所用的抗肿瘤药物，患者可相对较好地分为两组：第一组11例，主要发生在经烷化剂化疗的淋巴系统肿瘤（8例）之后（10例使用烷化剂）；第二组14例，发生在原发性血小板增多症（ET）或真性红细胞增多症（PV）之后，主要接受羟基脲（10例）、哌泊溴烷（8例）、32P（6例）治疗，但很少使用烷化剂（2例）。第一组11例患者中有10例发现-7/del 7q，而第二组14例患者中有3例（P = 0.0001）。因此，治疗相关病例在伴有17p-综合征的AML和MDS中占很高比例。它们与经典的tMDS和tAML有许多共同特征，包括距首例肿瘤的间隔时间长、通常有白血病前期以及-5/del 5q的频繁发生。此外，其中约一半发生在烷化剂治疗后，通常伴有-7/del 7q。然而，另一半主要发生在经羟基脲或其他非烷化剂治疗的ET或PV之后，通常没有-7/del 7q。这些发现进一步支持了tAML和tMDS中既往使用的药物与细胞遗传学重排之间可能存在的关系。
