Cauwelier B, Cavé H, Gervais C, Lessard M, Barin C, Perot C, Van den Akker J, Mugneret F, Charrin C, Pagès M P, Grégoire M-J, Jonveaux P, Lafage-Pochitaloff M, Mozzicconacci M J, Terré C, Luquet I, Cornillet-Lefebvre P, Laurence B, Plessis G, Lefebvre C, Leroux D, Antoine-Poirel H, Graux C, Mauvieux L, Heimann P, Chalas C, Clappier E, Verhasselt B, Benoit Y, Moerloose B D, Poppe B, Van Roy N, Keersmaecker K D, Cools J, Sigaux F, Soulier J, Hagemeijer A, Paepe A D, Dastugue N, Berger R, Speleman F
Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Leukemia. 2007 Jan;21(1):121-8. doi: 10.1038/sj.leu.2404410. Epub 2006 Oct 12.
Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRbeta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.
最近，我们和其他研究人员描述了一种新的染色体重排，即inv(7)(p15q34)和t(7;7)(p15;q34)，在5%的T细胞急性淋巴细胞白血病（T-ALL）患者中涉及T细胞受体β（TCRβ）（7q34）和HOXA基因座（7p15），导致特别是HOXA10的转录激活。为了进一步探讨这种染色体畸变的临床、免疫表型和分子遗传学发现，我们研究了另外330例T-ALL。这又发现了另外5例患者存在TCRβ-HOXA重排，使得424例患者中的总数达到14例（3.3%）。对170例T-ALL患者进行了HOXA10基因表达的实时定量PCR分析，在25.2%的病例中检测到HOXA10过表达，包括所有有TCRβ-HOXA重排的病例（8.2%）。相比之下，短HOXA10转录本HOXA10b的表达几乎只在TCRβ-HOXA重排的病例中发现，这表明HOXA10b短转录本在TCRβ-HOXA介导的肿瘤发生中具有特定作用。除了9p21缺失和NOTCH1激活突变分别存在于64%和67%的病例中外，在TCRβ-HOXA重排的病例中未检测到T-ALL亚型中常见的其他分子和/或细胞遗传学畸变（SIL-TAL1、CALM-AF10、HOX11、HOX11L2）。总之，本研究通过临床、免疫表型和分子遗传学特征将TCRβ-HOXA重排的T-ALL定义为一个独特的细胞遗传学亚组。
