Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
Ther Adv Hematol. 2013 Aug;4(4):298-308. doi: 10.1177/2040620713495639.
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the United States and one of the most heritable cancers. A family history of the disease is perhaps the best defined risk factor, and approximately 15-20% of CLL patients have a family member with CLL or a related lymphoproliferative disorder. Much effort has been devoted to trying to elucidate the mechanisms underlying this genetic risk. Familial CLL appears to be clinically and biologically similar to sporadic CLL, and most if not all CLL appears to be preceded by monoclonal B-cell lymphocytosis (MBL), which does appear to occur at higher frequency in relatives in families with CLL. Neither linkage studies nor candidate gene association studies have proven particularly informative in CLL, but genomewide association studies have identified multiple low-risk variants that together explain about 16% of the familial risk of CLL. Studies of individual families have identified higher-risk single nucleotide polymorphisms or copy number variants associated with disease risk in those families. Current efforts to identify additional risk loci are focused on applying next-generation sequencing to the germline of informative CLL families as well as individuals with sporadic CLL.
慢性淋巴细胞白血病（CLL）是美国最常见的白血病，也是最具遗传性的癌症之一。疾病家族史可能是最好定义的风险因素，约 15-20%的 CLL 患者有 CLL 或相关淋巴增生性疾病的家族成员。人们已经付出了很大的努力试图阐明这种遗传风险的机制。家族性 CLL 在临床上和生物学上似乎与散发性 CLL 相似，而且大多数（如果不是全部）CLL 似乎都发生在克隆性 B 细胞淋巴增生症（MBL）之前，而 MBL 在 CLL 家族的亲属中似乎更常发生。连锁研究和候选基因关联研究都没有在 CLL 中证明特别有意义，但全基因组关联研究已经确定了多个低风险变体，这些变体共同解释了 CLL 家族风险的约 16%。对个别家庭的研究已经确定了与这些家庭疾病风险相关的更高风险单核苷酸多态性或拷贝数变异。目前，确定额外风险位点的努力集中在将下一代测序应用于信息丰富的 CLL 家庭以及散发性 CLL 个体的种系上。
