Nguyen-Khac Florence, Chapiro Elise, Lesty Claude, Grelier Aurore, Luquet Isabelle, Radford-Weiss Isabelle, Lefebvre Christine, Fert-Ferrer Sandra, Callet-Bauchu Evelyne, Lippert Eric, Raggueneau Victoria, Michaux Lucienne, Barin Carole, Collonge-Rame Marie-Agnes, Mugneret Francine, Eclache Virginie, Taviaux Sylvie, Dastugue Nicole, Richebourg Steven, Struski Stéphanie, Talmant Pascaline, Baranger Laurence, Gachard Nathalie, Gervais Carine, Quilichini Benoit, Settegrana Catherine, Maloum Karim, Davi Frederic, Merle-Béral Hélène
Am J Blood Res. 2011;1(1):13-21. Epub 2011 Apr 15.
Chromosomal translocations are usually analyzed as a single entity, and are associated with a poor outcome in chronic lymphocytic leukemia. Translocations involving immunoglobulin genes are recurrent, but uncommon (<5%), and their individual prognosis is not clear. The two most frequent partners are BCL2 (18q21) and BCL3 (19q13).
Herein, 75 cases are reported of chronic lymphocytic leukemia and t(14;18) (BCL2-CLLs). Our series benefits from morphological, immunological and cytogenetical reviews. The IGHV status analyses were performed by referring laboratories. Comparison was made with our previously published series of chronic lymphocytic leukemia patients with t(14;19) (BCL3-CLLs, n=29).
Compared with BCL3-CLLs, lymphocytosis was lower in BCL2-CLLs (p<0.008), and splenomegaly was less frequent (p<0.0001). There were more "typical" morphologies (p<0.005) and Matutes scores >4 (p<0.001) in the BCL2-CLLs group, and less CD38 expression (p<0.04). More variant BCL2-translocations were observed (t(18;22), n=11; 2t(2;18), n=2; p<0.02), and BCL2-translocation was frequently single (p<0.002). Complex karyotypes (p<0.02), trisomy 12 (p<0.03), 6q deletion (p<0.002) and TP53 deletion (p<0.02) were less frequent in BCL2-CLLs, whereas 13q deletion was more frequent (p<0.005). The IGHV gene was frequently mutated in BCL2-CLLs (p<0.0001). Treatment-free survival was longer in BCL2-CLLs (p<0.0001).
BCL2-CLL.S express CD5 and lack expression of CD38, and have a Matutes score ≥4, frequent trisomy 12, no ATM and 6q deletions, and a mutated IGHV status. Compared to BCL3-CLLs, BCL2-CLLs are much less aggressive; indicating that identifying individual translocations and cytogenetic partners would allow improved patient stratification.
染色体易位通常作为一个单一实体进行分析，并且与慢性淋巴细胞白血病的不良预后相关。涉及免疫球蛋白基因的易位较为常见，但并不常见（<5%），其个体预后尚不清楚。两个最常见的伙伴基因是BCL2（18q21）和BCL3（19q13）。
本文报道了75例慢性淋巴细胞白血病和t(14;18)（BCL2-CLLs）病例。我们的系列研究受益于形态学、免疫学和细胞遗传学评估。IGHV状态分析由参考实验室进行。与我们之前发表的一系列慢性淋巴细胞白血病患者t(14;19)（BCL3-CLLs，n = 29）进行了比较。
与BCL3-CLLs相比，BCL2-CLLs的淋巴细胞增多症程度较低（p<0.008），脾肿大的发生率较低（p<0.0001）。BCL2-CLLs组有更多“典型”形态（p<0.005）和Matutes评分>4（p<0.001），且CD38表达较少（p<0.04）。观察到更多的BCL2变异易位（t(18;22)，n = 11；2t(2;18)，n = 2；p<0.02），且BCL2易位通常为单一易位（p<0.002）。复杂核型（p<0.02）、12号染色体三体（p<0.03）、6q缺失（p<0.002）和TP53缺失（p<0.02）在BCL2-CLLs中较少见，而13q缺失更常见（p<0.005）。IGHV基因在BCL2-CLLs中经常发生突变（p<0.0001）。BCL2-CLLs的无治疗生存期更长（p<0.0001）。
BCL2-CLLs表达CD5且缺乏CD38表达，Matutes评分≥4，经常出现12号染色体三体，无ATM和6q缺失，且IGHV状态发生突变。与BCL3-CLLs相比，BCL2-CLLs的侵袭性要小得多；这表明识别个体易位和细胞遗传学伙伴将有助于改善患者分层。
