Service d'Hématologie Biologique, Hôpital Pitié-Salpêtrière, Paris, France; INSERM U872, Centre de Recherche des Cordeliers, Paris, 6, France; UPMC, Paris, 6, France.
Genes Chromosomes Cancer. 2014 Mar;53(3):240-7. doi: 10.1002/gcc.22134. Epub 2013 Nov 30.
Whether sex chromosome loss (SCL) is an age-related phenomenon or a cytogenetic marker of hematological disease is unclear. To address this issue in chronic lymphocytic leukemia (CLL), we investigated 20 cases with X or Y chromosome loss detected by conventional cytogenetics (CC). The frequency of SCL was low in CLL (2.3%). It was the sole abnormality, as detected by CC, in 10/20 (50%) patients. Fluorescence in situ hybridization (FISH) analyses confirmed SCL in all patients tested, present in 5-88% of cells (median: 68%). Deletions of 13q were observed by FISH in 16/20 (80%) patients. Compared with CLL without SCL, SCL was significantly associated with 13q deletion, especially when bi-allelic (P = 0.04). Co-hybridization analyses showed that SCL could be a concomitant, primary or secondary change, or be present in an independent clone. FISH analyses were performed on blood sub-populations isolated by Ficoll or flow cytometry. Comparing mononuclear cells (including CLL cells) and polynuclear cells separated by Ficoll, a maximum of 2% of polynuclear cells were found with SCL, whereas mononuclear cells exhibited a significantly higher loss frequency (range: 6-87%) (P = 0.03). Comparing B-cells (including CLL cells) and T-cells sorted by flow cytometry, the proportion of B-CD19+ cells with SCL was significantly higher (range: 88-96%) than that observed in T-CD3+ cells (range: 2-6%) (P = 0.008). We conclude that SCL has to be considered as a clonal aberration in CLL that may participate in the oncogenic process.
性染色体丢失（SCL）是与年龄相关的现象还是血液系统疾病的细胞遗传学标志物尚不清楚。为了在慢性淋巴细胞白血病（CLL）中解决这个问题，我们研究了 20 例通过常规细胞遗传学（CC）检测到 X 或 Y 染色体丢失的病例。SCL 在 CLL 中的频率较低（2.3%）。在 20 例患者中，有 10 例（50%）仅通过 CC 检测到 SCL，这是唯一的异常。荧光原位杂交（FISH）分析证实了所有检测患者的 SCL 存在，在 5-88%的细胞中（中位数：68%）存在。FISH 在 20 例患者中的 16 例（80%）中观察到 13q 缺失。与没有 SCL 的 CLL 相比，SCL 与 13q 缺失显著相关，尤其是当双等位缺失时（P = 0.04）。共杂交分析表明，SCL 可以是伴随的、原发性或继发性改变，或者存在于独立的克隆中。FISH 分析在通过菲可尔或流式细胞术分离的血液亚群上进行。比较菲可尔分离的单核细胞（包括 CLL 细胞）和多形核细胞，最多有 2%的多形核细胞存在 SCL，而单核细胞的丢失频率明显更高（范围：6-87%）（P = 0.03）。比较通过流式细胞术分选的 B 细胞（包括 CLL 细胞）和 T 细胞，具有 SCL 的 B-CD19+细胞的比例明显高于 T-CD3+细胞（范围：88-96%比 2-6%）（P = 0.008）。我们得出结论，SCL 必须被视为 CLL 中的克隆异常，它可能参与致癌过程。
