Hôpital Saint-Louis, Paris, France.
Hematology Am Soc Hematol Educ Program. 2011;2011:492-7. doi: 10.1182/asheducation-2011.1.492.
Fanconi anemia (FA) is the most frequent inherited cause of BM failure (BMF). Fifteen FANC genes have been identified to date, the most prevalent being FANCA, FANCC, FANCG, and FANCD2. In addition to classical presentations with progressive BMF during childhood and a positive chromosome breakage test in the blood, atypical clinical and/or biological situations can be seen in which a FA diagnosis has to be confirmed or eliminated. For this, a range of biological tools have been developed, including analysis of skin fibroblasts. FA patients experience a strong selective pressure in the BM that predisposes to clonal evolution and to the emergence in their teens or young adulthood of myelodysplasia syndrome (MDS) and/or acute myeloid leukemia (AML) with a specific pattern of somatic chromosomal lesions. The cellular mechanisms underlying (1) the hematopoietic defect which leads to progressive BMF and (2) somatic clonal evolutions in this background, are still largely elusive. Elucidation of these mechanisms at the molecular and cellular levels should be useful to understand the physiopathology of the disease and to adapt the follow-up and treatment of FA patients. This may also ultimately benefit older, non-FA patients with aplastic anemia, MDS/AML for whom FA represents a model genetic condition.
范可尼贫血（FA）是骨髓衰竭（BMF）最常见的遗传性原因。迄今为止，已经确定了 15 个 FANC 基因，最常见的是 FANCA、FANCC、FANCG 和 FANCD2。除了在儿童期出现进行性 BMF 和血液中染色体断裂试验阳性的经典表现外，还可能出现不典型的临床和/或生物学情况，需要确认或排除 FA 诊断。为此，已经开发了一系列生物学工具，包括皮肤成纤维细胞分析。FA 患者在骨髓中经历强烈的选择压力，这容易导致克隆进化，并在十几岁或成年早期出现骨髓增生异常综合征（MDS）和/或急性髓系白血病（AML），并伴有特定的体细胞染色体病变模式。导致进行性 BMF 的造血缺陷和（2）在这种背景下的体细胞克隆进化的细胞机制在很大程度上仍未被阐明。阐明这些机制在分子和细胞水平上应该有助于理解疾病的病理生理学，并调整 FA 患者的随访和治疗。这最终也可能使患有再生障碍性贫血、MDS/AML 的年龄较大的非 FA 患者受益，FA 是这些患者的一种典型遗传疾病。
