Nardini Elena, Rizzi Simona, Capello Daniela, Vitolo Umberto, Gaidano Gianluca, Menard Sylvie, Balsari Andrea
Department of Experimental Oncology, Molecular Targeting Unit, National Cancer Institute, Via Venezian 1, 20133, Milan, Italy.
FEBS Lett. 2002 May 8;518(1-3):119-23. doi: 10.1016/s0014-5793(02)02672-8.
We investigated 38 cases of B-cell chronic lymphocytic leukemia (B-CLL) for the presence of non-productive rearrangements in the S(mu) regions and defined for the first time the molecular nature of these rearrangements. Southern blot analysis revealed S(mu) region rearrangements in 13 cases (34%) and polymerase chain reactions (PCRs) indicated that these rearrangements consisted of internal deletions of the S(mu) region. Long-distance PCRs localized the S(mu) deletions in the V(H)DJ(H) rearranged allele in most cases. We investigated if S(mu) deletions were related to V(H) somatic mutations that, together with isotype switch recombination, are indicative of the B-cell maturation stage. No significant correlation between the presence of S(mu) deletions and V(H) somatic mutations was found, indicating that the two processes are independent in B-CLL. Moreover no significant correlation between S(mu) deletions and prognosis was observed. Having shown that S(mu) internal deletions are not chromosome translocations rules out their involvement in the onset of malignancy, while their localization in the V(H)DJ(H) rearranged alleles suggests a possible role in the stabilization of the isotype of the expressed immunoglobulin.
我们研究了38例B细胞慢性淋巴细胞白血病（B-CLL）患者，以检测其S（μ）区域是否存在无效重排，并首次明确了这些重排的分子性质。Southern印迹分析显示，13例（34%）患者存在S（μ）区域重排，聚合酶链反应（PCR）表明这些重排由S（μ）区域的内部缺失组成。在大多数情况下，长距离PCR将S（μ）缺失定位在V（H）DJ（H）重排等位基因中。我们研究了S（μ）缺失是否与V（H）体细胞突变有关，V（H）体细胞突变与同种型转换重组一起可指示B细胞成熟阶段。未发现S（μ）缺失与V（H）体细胞突变之间存在显著相关性，这表明这两个过程在B-CLL中是独立的。此外，未观察到S（μ）缺失与预后之间存在显著相关性。已证明S（μ）内部缺失不是染色体易位，排除了它们参与恶性肿瘤发生的可能性，而它们在V（H）DJ（H）重排等位基因中的定位表明其可能在稳定表达的免疫球蛋白同种型中发挥作用。
