De Angeli C, Gandini D, Cuneo A, Moretti S, Bigoni R, Roberti M G, Bardi A, Castoldi G L, del Senno L
Centro Interdipartimentale di Biotecnologie-Sezione di Studi Biochimici delle Patologie del Genoma Umano; Università degli Studi, Ferrara, Italy.
Haematologica. 2000 Sep;85(9):913-21.
The translocation t(11;14) (q13;q32), typically described in mantle cell lymphomas (MCL), has also been found in some cases of non-MCL lymphoproliferative disorders, such as splenic lymphoma with villous lymphocytes (SLVL), multiple myeloma (MM), prolymphocytic leukemia (PLL), typical and atypical chronic lymphocytic leukemia (CLL and aCLL). In order to define better the genetic features of aCLL with t(11;14), which could represent a distinct disease subset, we looked for genetic lesions in the BCL-1 locus and in BCL-2, BCL-6, c-myc and p53 genes.
We investigated a panel of B-lymphoproliferative disorders with translocation t(11;14)(q13;q32) including nine aCLL, six MCL and one MM. Southern and Northern blot analysis was used to investigate DNA structure and RNA expression; SSCP and direct sequencing were used to detect and characterize p53 point mutations; cytofluorimetric analysis was used to quantify p53 protein.
Alterations of BCL-2, BCL-6 and c-myc were not detected. Conversely, BCL-1 rearrangements were present in 4 out of 7 aCLL and in 2 out of 4 MCL. A high incidence of p53 gene alterations was found, almost equivalent in aCLL and MCL.
Our results indicate that the occurrence of BCL-1 locus lesions in aCLL selected for t(11;14) is as high as in MCL. Interestingly, rearrangements in the mTC1 (minor translocation cluster 1) were only found in aCLL. Therefore, the two B-cell chronic lymphoproliferative disorders share similar molecular rearrangements and the t(11;14) identifies a subset of B-CLL sharing molecular features with MCL and characterized by aggressive clinical evolution.
11号和14号染色体易位（t(11;14)(q13;q32)）通常见于套细胞淋巴瘤（MCL），但在某些非MCL淋巴增殖性疾病中也有发现，如伴有绒毛状淋巴细胞的脾淋巴瘤（SLVL）、多发性骨髓瘤（MM）、原淋巴细胞白血病（PLL）、典型和非典型慢性淋巴细胞白血病（CLL和aCLL）。为了更好地界定伴有t(11;14)的aCLL的遗传特征（其可能代表一个独特的疾病亚组），我们探寻了BCL-1基因座以及BCL-2、BCL-6、c-myc和p53基因中的遗传损伤。
我们研究了一组伴有t(11;14)(q13;q32)易位的B淋巴细胞增殖性疾病，包括9例aCLL、6例MCL和1例MM。采用Southern和Northern印迹分析来研究DNA结构和RNA表达；采用单链构象多态性（SSCP）和直接测序来检测和鉴定p53点突变；采用细胞荧光分析来定量p53蛋白。
未检测到BCL-2、BCL-6和c-myc的改变。相反，7例aCLL中有4例以及4例MCL中有2例存在BCL-1重排。发现p53基因改变的发生率较高，在aCLL和MCL中几乎相当。
我们的结果表明，在因t(11;14)而被挑选出的aCLL中，BCL-1基因座损伤的发生率与MCL中一样高。有趣的是，仅在aCLL中发现了小易位簇1（mTC1）中的重排。因此，这两种B细胞慢性淋巴细胞增殖性疾病具有相似的分子重排，并且t(11;14)确定了一个B-CLL亚组，其与MCL具有共同的分子特征，并以侵袭性临床病程为特点。
