Mehta Parinda A, Harris Richard E, Davies Stella M, Kim Mi-Ok, Mueller Robin, Lampkin Beatrice, Mo Jun, Myers Kasiani, Smolarek Teresa A
Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Cancer Genet Cytogenet. 2010 Dec;203(2):180-6. doi: 10.1016/j.cancergencyto.2010.07.127.
Fanconi Anemia (FA) is an inherited bone marrow failure syndrome characterized by congenital abnormalities, progressive marrow failure and predisposition to myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and solid tumors. The most common acquired chromosomal aberrations in FA patients are trisomy of 1q and monosomy of chromosome 7; the latter is known to be associated with poor prognosis. A few reports also suggest that gains of 3q are associated with progression to MDS-AML and overall poor prognosis. It is not uncommon for patients with Fanconi anemia to have easily detectable (oligoclonal) chromosomal alterations in their still normal (nonmalignant) marrow, which makes it even more challenging to determine the import of such alterations. We conducted a retrospective longitudinal analysis of fluorescent in situ hybridization (FISH) analysis for gains in 1q and 3q and for monosomy 7 and 7q deletions on 212 bone marrow samples from 77 children with FA treated at our institution between 1987 and 2007. Given the baseline increased chromosomal instability and defective DNA repair in patients with FA, which leads to unbalanced chromosomal aberrations such as deletions, insertions, and translocations, for the purpose of this analysis an abnormal clone was defined as ≥10% abnormal cells. Chromosome 3 and 7 aberrations were associated with increased risk of developing MDS-AML (P = 0.019 and P < 0.001 respectively), although the significance of chromosome 3 aberrations disappeared when different observation times were accounted for. Gain of 1q alone did not predict development of MDS-AML. In conclusion, children with FA should be followed closely with FISH analyses, because some of the clonal chromosomal abnormalities may be early indicators of progression toward MDS-AML and thus also of the need for hematopoietic stem cell transplantation.
范可尼贫血（FA）是一种遗传性骨髓衰竭综合征，其特征为先天性异常、进行性骨髓衰竭，以及易患骨髓增生异常综合征（MDS）、急性髓系白血病（AML）和实体瘤。FA患者最常见的后天性染色体畸变是1q三体和7号染色体单体；后者已知与预后不良有关。一些报告还表明，3q的增加与进展为MDS-AML及总体预后不良有关。范可尼贫血患者在其仍正常（非恶性）的骨髓中存在易于检测到的（寡克隆）染色体改变并不罕见，这使得确定此类改变的意义更具挑战性。我们对1987年至2007年在我们机构接受治疗的77名FA儿童的212份骨髓样本进行了回顾性纵向荧光原位杂交（FISH）分析，以检测1q和3q的增加以及7号染色体单体和7q缺失。鉴于FA患者基线时染色体不稳定性增加和DNA修复缺陷，这会导致缺失、插入和易位等不平衡染色体畸变，为了本分析的目的，异常克隆定义为≥10%的异常细胞。3号和7号染色体畸变与发生MDS-AML的风险增加相关（分别为P = 0.019和P < 0.001），尽管在考虑不同观察时间时3号染色体畸变的意义消失了。单独的1q增加并不能预测MDS-AML的发生。总之，FA儿童应通过FISH分析密切随访，因为一些克隆性染色体异常可能是向MDS-AML进展的早期指标，因此也是造血干细胞移植需求的早期指标。
