The expression of 70 apoptosis genes in relation to lineage, genetic subtype, cellular drug resistance, and outcome in childhood acute lymphoblastic leukemia
The expression of 70 apoptosis genes in relation to lineage, genetic subtype, cellular drug resistance, and outcome in childhood acute lymphoblastic leukemia
复制标题
DOI：
10.1182/blood-2005-07-2930
复制
发表时间：
2006-01-15
期刊：
影响因子：
20.3
通讯作者：
Pieters, R
中科院分区：
文献类型：
--
作者：
Holleman, A;den Boer, ML;Pieters, R
儿童急性淋巴细胞白血病 (ALL) 由各种亚型组成，这些亚型对细胞毒性药物的反应不同，因此具有明显不同的临床结果。我们使用微阵列来研究 190 名初次诊断的 ALL 儿童中，70 个关键凋亡基因在按谱系、遗传亚型、体外耐药性和临床结果定义的白血病亚组之间是否存在差异表达。 70 个基因中的 44 个基因的表达在 T 系与 B 系 ALL 中存在显着差异，22 个基因在超二倍体与非超二倍体中存在显着差异，16 个基因在 TEL-AML1 阳性与阴性中存在差异，13 个在 E2A 重排与种系 B 系 ALL 中存在差异。 MCL1和DAPK1的表达与泼尼松龙敏感性显着相关，而BCL2L13、HRK和TNF与L-天冬酰胺酶耐药性相关。 BCL2L13 过度表达也与不利的临床结果相关 (P < .001)。包括已知危险因素在内的多变量分析显示，BCL2L13 表达是一个独立的预后因素 (P = .011)。在 St Jude 采用不同方案治疗的 92 名 ALL 儿童组成的验证组中也观察到了相同的趋势 (P = .051)。总之，ALL 亚型具有独特的凋亡基因表达模式，我们的数据表明选择性基因与儿童 B 系 ALL 的细胞耐药性和预后相关。
Childhood acute lymphoblastic leukemia (ALL) consists of various subtypes that respond differently to cytotoxic drugs and therefore have a markedly different clinical outcome. We used microarrays to investigate, in 190 children with ALL at initial diagnosis, whether 70 key apoptosis genes were differentially expressed between leukemic subgroups defined by lineage, genetic subtype, in vitro drug resistance, and clinical outcome. The expression of 44 of 70 genes was significantly different in T- versus B-lineage ALL, 22 genes differed in hyperdiploid versus nonhyperdiploid, 16 in TEL-AML1-positive versus-negative, and 13 in E2A-rearranged versus germ-line B-lineage ALL. Expression of MCL1 and DAPK1 was significantly associated with prednisolone sensitivity, whereas BCL2L13, HRK, and TNF were related to L-asparaginase resistance. BCL2L13 overexpression was also associated with unfavorable clinical outcome (P < .001). Multivariate analysis including known risk factors revealed that BCL2L13 expression was an independent prognostic factor (P = .011). The same trend was observed in a validation group of 92 children with ALL treated on a different protocol at St Jude (P = .051). In conclusion, ALL subtypes have a unique expression pattern of apoptosis genes and our data suggest that selective genes are linked to cellular drug resistance and prognosis in childhood B-lineage ALL.