Significance of Bone Marrow Karyotypes in Patients with

遗传性骨髓衰竭综合征（IBMFS）是一组罕见的遗传性疾病，具有独特的表型和实验室异常。患有IBMFS的患者，包括范可尼贫血（FA）、Diamond-Blackfan贫血（DBA）、Shwachman-Diamond综合征（SDS）和先天性角化不良（DC），发生再生障碍性贫血（AA）、骨髓增生异常综合征（MDS）和急性髓性白血病（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、系列、常规和分子细胞遗传学分析。我们假设骨髓核型异常，没有其他MDS的证据（显著的血细胞减少或形态发育不良），可能不能预测不良结局。分析包括集中审查的骨髓形态学、G带核型分析、荧光原位杂交（FISH）和比较基因组杂交（CGH）。患者已随访长达5年。13例FA患者中有6例（46%）检测到克隆性染色体异常，14例DBA患者中无一例（0%），4例SDS患者中有2例（50%），6例DC患者中有2例（33%）。G显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2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。1例骨髓核型正常的FA患者发生了形态学MDS。在5例FA患者中，3例患者的异常克隆先于具有临床意义的MDS。此外，在两名FA患者中，异常克隆的大小有增有减，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，以确定这些罕见疾病中细胞遗传学单独的预后意义，并结合骨髓形态学和临床评估。

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 five years. Clonal chromosome abnormalities have been detected in six of 13 (46 percent) patients with FA, none of 14 (0 percent) patients with DBA, two of four (50 percent) patients with SDS, and two of six (33 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.