Significance of Bone Marrow Karyotypes in Patients with

遗传性骨髓衰竭综合征（IBMFS）是一种异质性的罕见遗传疾病，具有独特的表型和实验室异常。IBMFS患者，包括Fanconi贫血（FA）、Diamond-Blackfan贫血（DBA）、Shwachman-Diamond综合征（SDS）和先天性角化不良症（DC），发生再生障碍性贫血（AA）、骨髓增生异常综合征（MDS）和急性髓系白血病（AML）的风险增加。为了确定IBMFS患者骨髓核型异常的发生率、类型和可能的临床意义，我们对骨髓进行了前瞻性、序列性、常规性和分子细胞遗传学分析。我们假设骨髓核型异常，如果没有MDS的其他证据（明显的细胞减少或形态发育不良），可能不能预测不良结果。分析包括中央审查骨髓形态，g带核型分析，荧光原位杂交（FISH）和比较基因组杂交（CGH）。研究人员对患者进行了长达四年的随访。12例FA患者中有5例（42%）检测到克隆染色体异常，14例DBA患者中无克隆染色体异常（0%），2例SDS患者中有2例（100%），3例DC患者中有2例（67%）检测到克隆染色体异常。g带是检测异常克隆的最佳方法，FISH提供了额外的信息；CGH是最不敏感的方法。除了两例FA患者的单体7外，异常类型与新发MDS患者中常见的异常类型不同。一名骨髓核型正常的FA患者发展为形态学MDS。在5例FA患者中，有3例的异常克隆先于临床显著MDS。此外，在两名FA患者中，异常克隆在大小上忽大忽小，甚至消失。这些初步数据表明，IBMFS患者的异常骨髓核型可能与其他新发MDS患者不同，并支持需要大型协作数据库，以确定细胞遗传学单独，骨髓形态学和临床评估在这些罕见疾病中的预后意义。

The inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of rare genetic disorders with distinctive phenotypic and laboratory abnormalities. Patients with IBMFS, including Fanconi Anemia (FA), Diamond-Blackfan Anemia (DBA), Shwachman-Diamond Syndrome (SDS), and Dyskeratosis Congenita (DC), have an increased risk of developing aplastic anemia (AA), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). To determine the incidence, types, and possible clinical significance of abnormal bone marrow karyotypes among patients with IBMFS, we are conducting prospective, serial, routine and molecular cytogenetic analyses of marrow. We hypothesize that abnormal marrow karyotypes, without other evidence of MDS (significant cytopenias or morphologic dyspoiesis), may not predict an adverse outcome. Analyses have included centrally-reviewed marrow morphology, G-banded karyotype analysis, fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH). Patients have been followed for up to four years. Clonal chromosome abnormalities have been detected in five of 12 (42 percent) patients with FA, none of 14 (0 percent) patients with DBA, two of two (100 percent) patients with SDS, and two of three (67 percent) patients with DC. G-banding is the best method for detecting abnormal clones, and FISH provides additional information; CGH is the least sensitive method. With the exception of monosomy 7 in two patients with FA, the types of abnormalities differ from those commonly seen in patients with de novo MDS. One FA patient with a normal marrow karyotype has developed morphologic MDS. Abnormal clones preceded clinically significant MDS in three of the five patients with FA. Furthermore, the abnormal clones have waxed and waned in size, and even disappeared, in two of the FA patients. These preliminary data suggest that abnormal marrow karyotypes in patients with IBMFS may differ from other patients with de novo MDS, and support the need for large collaborative databases in order to determine the prognostic significance of cytogenetics alone, and combined with marrow morphology and clinical assessment, in these rare disorders.