Familiades J, Bousquet M, Lafage-Pochitaloff M, Béné M-C, Beldjord K, De Vos J, Dastugue N, Coyaud E, Struski S, Quelen C, Prade-Houdellier N, Dobbelstein S, Cayuela J-M, Soulier J, Grardel N, Preudhomme C, Cavé H, Blanchet O, Lhéritier V, Delannoy A, Chalandon Y, Ifrah N, Pigneux A, Brousset P, Macintyre E A, Huguet F, Dombret H, Broccardo C, Delabesse E
INSERM U563, Toulouse, France.
Leukemia. 2009 Nov;23(11):1989-98. doi: 10.1038/leu.2009.135. Epub 2009 Jul 9.
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.
成人和儿童B细胞祖细胞急性淋巴细胞白血病（BCP-ALL）在发病率和预后方面存在差异。这些差异主要归因于与这两种临床实体相关的分子异常。最近一项使用寡核苷酸SNP阵列的全基因组分析表明，PAX5（配对盒结构域5）是儿童BCP-ALL体细胞突变的主要靶点，在38.9%的病例中发生改变。我们在此报告了在独特的临床方案GRAALL-2003/GRAAPH-2003中对117例成人BCP-ALL患者PAX5编码序列改变的最广泛分析。我们的研究表明，34%的成人BCP-ALL中PAX5发生突变，突变形式为部分或完全缺失、部分或完全扩增、点突变或融合基因。PAX5改变具有异质性，17%的病例为完全缺失，10%为局灶性缺失，7%为点突变，1%为易位。PAX5完全缺失和PAX5点突变有所不同。PAX5完全缺失似乎是一个继发事件，与BCR-ABL1或TCF3-PBX1融合基因以及较低的白细胞计数显著相关。
