Cavazzini Francesco, Hernandez Jose Angel, Gozzetti Alessandro, Russo Rossi Antonella, De Angeli Cristiano, Tiseo Ruana, Bardi Antonella, Tammiso Elisa, Crupi Rosaria, Lenoci Maria Pia, Forconi Francesco, Lauria Francesco, Marasca Roberto, Maffei Rossana, Torelli Giuseppe, Gonzalez Marcos, Martin-Jimenez Patricia, Maria Hernandez Jesus, Rigolin Gian Matteo, Cuneo Antonio
Section of Haematology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Ferrara, Italy.
Br J Haematol. 2008 Aug;142(4):529-37. doi: 10.1111/j.1365-2141.2008.07227.x. Epub 2008 Jun 28.
Immunophenotypic studies, fluorescence in situ hybridization (FISH) and conventional karyotyping were used to define the clinicobiological significance of 14q32 translocations involving the immunoglobulin gene locus (14q32/IGH) in 252 chronic lymphocytic leukaemia (CLL) patients. The following regions were studied: 13q14, centromere 12, 6q21; 11q22/ATM; 17p13/TP53, 14q32/IGH. Patients were classified as group 1 (favourable, i.e. 13q-single or normal), group 2 (intermediate risk, i.e. +12, 6q-, 1-2 anomalies), group 3 (unfavourable, i.e. 17p-, 11q-, complex karyotype), or group 4 (14q32/IGH translocation). Endpoints were treatment-free survival (TFS) and overall survival (OS). One hundred and ten patients were included in group 1, 99 in group 2, 25 in group 3 and 18 in group 4. 14q32/IGH translocation partners were identified in eight cases (BCL2 in five cases, BCL11A, CCND3 and CDK6 in one case each). group 4 showed shorter TFS versus groups 2 and 1 (25% patients treated at 2 months vs. 12 (P = 0.02) and 20 months (P = 0.002), respectively) and shorter OS (25% patients dead at 18 months versus 50 (P = 0.0003) and >60 months (P < 0.0001) respectively. The 14q32/IGH translocation maintained prognostic significance at multivariate analysis on TFS (P = 0.025) and OS (P < 0.001), along with advanced stage and CD38+. These findings show that the 14q32/IGH translocation predicts for an unfavourable outcome in CLL and that this cytogenetic subset might be included as a separate entity in a hierarchical cytogenetic classification of CLL.
采用免疫表型研究、荧光原位杂交（FISH）和传统核型分析，以确定252例慢性淋巴细胞白血病（CLL）患者中涉及免疫球蛋白基因位点（14q32/IGH）的14q32易位的临床生物学意义。研究了以下区域：13q14、12号染色体着丝粒、6q21；11q22/ATM；17p13/TP53、14q32/IGH。患者被分为1组（预后良好，即孤立13q-或核型正常）、2组（中危，即+12、6q-、1-2个异常）、3组（预后不良，即17p-、11q-、复杂核型）或4组（14q32/IGH易位）。观察终点为无治疗生存期（TFS）和总生存期（OS）。1组纳入110例患者，2组99例，3组25例，4组18例。在8例患者中鉴定出14q32/IGH易位伙伴（5例为BCL2，1例分别为BCL11A、CCND3和CDK6）。与2组和1组相比，4组的TFS较短（2个月时25%的患者接受治疗，而2组为12个月（P = 0.02），1组为20个月（P = 0.002）），OS也较短（18个月时25%的患者死亡，而2组为50个月（P = 0.0003），1组>60个月（P < 0.0001））。在TFS（P = 0.025）和OS（P < 0.001）的多因素分析中，14q32/IGH易位与晚期和CD38+一起保持预后意义。这些发现表明，14q32/IGH易位预示CLL预后不良，并且这个细胞遗传学亚组可能作为一个单独的实体纳入CLL的分层细胞遗传学分类中。
