Section of Hematology, Department of Biomedical Sciences, University of Ferrara, Ferrara, Italy.
Leuk Lymphoma. 2012 Jan;53(1):83-8. doi: 10.3109/10428194.2011.606384. Epub 2011 Sep 13.
To better define the significance of clonal evolution (CE) including 14q32 translocations involving the immunoglobulin heavy chain gene (IGH) in chronic lymphocytic leukemia (CLL), 105 patients were analyzed sequentially by fluorescence in situ hybridization (FISH) with the following panel of probes: 13q14/D13S25, 11q22/ATM, 17p13/TP53, #12-centromere and 14q32/IGH break-apart probe. CE was observed in 15/105 patients after 24-170 months (median 64). Recurring aberrations at CE were 14q32/IGH translocation in seven patients; other aberrations were 17p -, 11q -, biallelic 13q - and 14q32 deletion. CE was detected in 15/58 pre-treated patients; in contrast, none of 47 untreated patients developed CE (p < 0.0001). In two cases the appearance of 14q32/IGH translocation was first detected in the bone marrow (BM) or in the lymph node (LN) and 13-58 months later in the peripheral blood (PB). ZAP70 + and high-risk cytogenetics predicted for the occurrence of CE with borderline statistical significance (p = 0.055 and 0.07, respectively). Shorter time to first treatment (TTT) and time to chemorefractoriness (TTCR) were noted in 15 patients with CE when compared to patients without CE (TTT: 35 vs. 71 months, p = 0.0033 and TTCR: 34 vs. 86 months, p = 0.0046, respectively). Survival after the development of CE was 32 months (standard error 8.5). We arrived at the following conclusions: (i) 14q32/IGH translocation may represent one of the most frequent aberrations acquired during the natural history of CLL and (ii) it may be detected earlier in BM or LN samples; (iii) CE including 14q32/IGH translocation occurs in pre-treated patients with short TTT and TTCR; (iii) survival after CE is relatively short.
为了更好地定义克隆进化（CE）的意义，包括涉及免疫球蛋白重链基因（IGH）的 14q32 易位在慢性淋巴细胞白血病（CLL）中的意义，对 105 例患者进行了连续荧光原位杂交（FISH）分析，使用以下探针组合：13q14/D13S25、11q22/ATM、17p13/TP53、#12-着丝粒和 14q32/IGH 分离探针。在 24-170 个月（中位数 64）后，在 15/105 例患者中观察到 CE。CE 时反复出现的异常包括 7 例患者的 14q32/IGH 易位；其他异常包括 17p-、11q-、双等位基因 13q-和 14q32 缺失。在 15/58 例预处理患者中检测到 CE；相比之下，47 例未治疗患者中均未出现 CE（p<0.0001）。在两种情况下，14q32/IGH 易位的出现最初在骨髓（BM）或淋巴结（LN）中检测到，13-58 个月后在外周血（PB）中检测到。ZAP70+和高风险细胞遗传学对 CE 的发生具有边缘统计学意义（p=0.055 和 0.07）。与无 CE 的患者相比，在 15 例有 CE 的患者中，首次治疗时间（TTT）和化疗耐药时间（TTCR）更短（TTT：35 对 71 个月，p=0.0033 和 TTCR：34 对 86 个月，p=0.0046）。CE 发生后的生存时间为 32 个月（标准误差 8.5）。我们得出以下结论：（i）14q32/IGH 易位可能代表 CLL 自然史中获得的最常见异常之一；（ii）它可能更早地在 BM 或 LN 样本中检测到；（iii）CE 包括 14q32/IGH 易位发生在 TTT 和 TTCR 较短的预处理患者中；（iii）CE 后的生存时间相对较短。
