Maloum K, Davi F, Magnac C, Pritsch O, McIntyre E, Valensi F, Binet J L, Merle-Béral H, Dighiero G
Department of d'Hématologie, CHU Pitié-Salpêtrière, Paris.
Blood. 1995 Nov 15;86(10):3883-90.
In contrast to highly mutated follicular lymphomas and multiple myelomas, chronic lymphocytic leukemias (CLLs) frequently express VH genes in germline configuration. It is currently unclear whether this difference is related to the expression of CD5 or to the differentiation stage of the B cell when malignant transformation occurs. We have studied the VH sequence of 11 cases of CD5- B-CLL to address the question whether CD5- B-CLL are derived from naive pregerminal B cells (low mutation pattern) or from germinal center-derived memory B cells (high mutation pattern). Among the 12 detected rearrangements (2 distinct rearrangements in 1 case) VH1 family was found in 2, VH2 in 2, VH3 in 4, and VH4 in 4. Nine different VH genes were detected among the 12 rearrangements, including 2 cases expressing V1-69 (51p1) and 1 case expressing V4-39 (VH4.18), previously reported to be overexpressed in CD5+ B-CLL. A higher mutation pattern, following a random distribution, was observed when compared with classical CD5+ B-CLL. However, as reported in normal B cells, these results appeared to be related to membrane Ig phenotype (less mutations in membrane mu delta-expressing forms in leukemias expressing exclusively membrane mu). Overall, the differences found when comparing the mutational profile with classical CD5+ B-CLL were not clearcut and might be explained more by the membrane isotype (mu v mu delta) than by CD5 expression.
与高度突变的滤泡性淋巴瘤和多发性骨髓瘤不同，慢性淋巴细胞白血病（CLL）常以种系构型表达VH基因。目前尚不清楚这种差异是与CD5的表达有关，还是与恶性转化发生时B细胞的分化阶段有关。我们研究了11例CD5 - B - CLL的VH序列，以探讨CD5 - B - CLL是源自未成熟的生发前B细胞（低突变模式）还是源自生发中心来源的记忆B细胞（高突变模式）这一问题。在检测到的12种重排中（1例中有2种不同重排），发现VH1家族有2种，VH2有2种，VH3有4种，VH4有4种。在12种重排中检测到9种不同的VH基因，包括2例表达V1 - 69（51p1）和1例表达V4 - 39（VH4.18），此前报道这两种基因在CD5 + B - CLL中过表达。与经典的CD5 + B - CLL相比，观察到更高的突变模式，且呈随机分布。然而，正如在正常B细胞中所报道的那样，这些结果似乎与膜Ig表型有关（在仅表达膜μ的白血病中，表达膜μδ的形式突变较少）。总体而言，与经典CD5 + B - CLL相比，在突变谱中发现的差异并不明确，可能更多地是由膜同种型（μ对μδ）而非CD5表达来解释。
