PAX5 mutations occur frequently in adult B-cell progenitor acute lymphoblastic leukemia and PAX5 haploinsufficiency is associated with BCR-ABL1 and TCF3-PBX1 fusion genes: a GRAALL study
PAX5 mutations occur frequently in adult B-cell progenitor acute lymphoblastic leukemia and PAX5 haploinsufficiency is associated with BCR-ABL1 and TCF3-PBX1 fusion genes: a GRAALL study
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DOI：
10.1038/leu.2009.135
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发表时间：
2009-11-01
期刊：
影响因子：
11.4
通讯作者：
Delabesse, E.
中科院分区：
文献类型：
--
作者：
Familiades, J.;Bousquet, M.;Delabesse, E.
成人和儿童B细胞祖细胞急性淋巴细胞白血病(BCP-ALL)的发病率和预后不同。这些差异主要是由于与这两个临床实体相关的分子异常所致。最近使用寡核苷酸多态性阵列进行的全基因组分析表明，PAX5(配对盒区5)是儿童BCP体细胞突变的主要目标-在38.9%的病例中都发生了改变。我们在这里报道了在独特的临床方案GRAALL-2003/GRAAPH-2003中对117例成人BCP-ALL患者的PAX5编码序列改变进行的最广泛的分析。我们的研究表明，PAX5在34%的成人BCP-ALL中发生突变，突变包括部分或完全缺失、部分或完全扩增、点突变或融合基因。Pax5的改变是异质性的，包括17%的完全丢失，10%的局灶性缺失，7%的点突变和1%的易位。Pax5完全缺失和PAX5点突变不同。Pax5完全缺失似乎是一个次要事件，与BCR-ABL1或TCF3-Pbx1融合基因和白细胞计数降低显著相关。白血病(2009年)23,1989年至1998年；doi：10.1038/leu，2009.135；在线发布
Adult and child B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) differ in terms of incidence and prognosis. These disparities are mainly due to the molecular abnormalities associated with these two clinical entities. A genome-wide analysis using oligo SNP arrays recently demonstrated that PAX5 (paired-box domain 5) is the main target of somatic mutations in childhood BCP-ALL being altered in 38.9% of the cases. We report here the most extensive analysis of alterations of PAX5 coding sequence in 117 adult BCP-ALL patients in the unique clinical protocol GRAALL-2003/GRAAPH-2003. Our study demonstrates that PAX5 is mutated in 34% of adult BCP-ALL, mutations being partial or complete deletion, partial or complete amplification, point mutation or fusion gene. PAX5 alterations are heterogeneous consisting in complete loss in 17%, focal deletions in 10%, point mutations in 7% and translocations in 1% of the cases. PAX5 complete loss and PAX5 point mutations differ. PAX5 complete loss seems to be a secondary event and is significantly associated with BCR-ABL1 or TCF3-PBX1 fusion genes and a lower white blood cell count. Leukemia (2009) 23, 1989-1998; doi: 10.1038/leu.2009.135; published online 9 July 2009