Moorman A V, Raimondi S C, Pui C H, Baruchel A, Biondi A, Carroll A J, Forestier E, Gaynon P S, Harbott J, Harms D O, Heerema N, Pieters R, Schrappe M, Silverman L B, Vilmer E, Harrison C J
Leukaemia Research Fund Cytogenetics Group, Cancer Sciences Division, University of Southampton, Southampton General Hospital, Southampton, UK.
Leukemia. 2005 Apr;19(4):557-63. doi: 10.1038/sj.leu.2403695.
This study characterized the additional chromosomal abnormalities (ACA) associated with 11q23 rearrangements in 450 infants and children with acute lymphoblastic leukemia (ALL) and examined the impact of these ACA on survival. Overall, 213 (47%) cases had ACA but the incidence varied according to patient age and 11q23 subgroup. Infants and patients with t(4;11)(q21;q23) had the lowest incidence of ACA (50/182 (27%) and 57/216 (26%) respectively), whereas patients with del(11)(q23) had the highest incidence (66/93 (71%)). Del(11)(q23) abnormalities were heterogeneous and occasionally secondary to t(9;22)(q34;q11.2). Thus, patients with del(11)(q23) comprised a separate biological entity, which was clearly distinct from those with an 11q23 translocation. The most frequent specific ACA were trisomy X (n = 38), abnormal 12p (n = 32), abnormal 9p (n = 28) and del(6q) (n = 19). The presence of ACA did not change the 5 year event-free survival estimates among children (56% (95% Cl 46-65%) vs 62% (54-69%)) or infants (22% (15-29%) vs 18% (9-29%)), nor when the different 11q23 subgroups were analyzed separately. This study has conclusively demonstrated that there is no prognostic effect of secondary chromosomal changes in association with 11q23 abnormalities in childhood ALL. However, characterization of these ACA is important to determine their potential role in initiation of MLL driven leukemogenesis.
本研究对450例急性淋巴细胞白血病(ALL)婴幼儿及儿童中与11q23重排相关的额外染色体异常(ACA)进行了特征分析,并研究了这些ACA对生存的影响。总体而言,213例(47%)病例存在ACA,但发病率因患者年龄和11q23亚组而异。婴儿及t(4;11)(q21;q23)患者的ACA发病率最低(分别为50/182(27%)和57/216(26%)),而del(11)(q23)患者的发病率最高(66/93(71%))。del(11)(q23)异常具有异质性,偶尔继发于t(9;22)(q34;q11.2)。因此,del(11)(q23)患者构成了一个独立的生物学实体,与11q23易位患者明显不同。最常见的特定ACA为X三体(n = 38)、12p异常(n = 32)、9p异常(n = 28)和del(6q)(n = 19)。ACA的存在并未改变儿童(56%(95%CI 46 - 65%)对62%(54 - 69%))或婴儿(22%(15 - 29%)对18%(9 - 29%))的5年无事件生存率估计,单独分析不同的11q23亚组时也是如此。本研究最终表明,儿童ALL中与11q23异常相关的继发性染色体改变无预后影响。然而,对这些ACA进行特征分析对于确定它们在MLL驱动的白血病发生起始中的潜在作用很重要。