Significance of Bone Marrow Karyotypes in Patients with

患者骨髓核型的意义

• 批准号: 7338735
• 负责人: diane c arthur
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7338735
• 关键词: Significance; Bone; Marrow; Karyotypes; Patients

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.

遗传性骨髓衰竭综合征 (IBMFS) 是一组异质性罕见遗传性疾病，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 (DC)，患再生障碍性贫血 (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 患者异常骨髓核型的发生率、类型和可能的临床意义，我们正在对骨髓进行前瞻性、系列、常规和分子细胞遗传学分析。我们假设，如果没有其他 MDS 证据（显着血细胞减少或形态学发育不良），异常的骨髓核型可能无法预测不良结果。分析包括集中审查的骨髓形态、G 带核型分析、荧光原位杂交 (FISH) 和比较基因组杂交 (CGH)。对患者进行了长达五年的随访。 13 名 FA 患者中有 6 名（46%）检测到克隆染色体异常，14 名 DBA 患者中没有检测到克隆染色体异常（0%），4 名 SDS 患者中有 2 名（50%），6 名 DC 患者中有 2 名（33%）。 G显带是检测异常克隆的最佳方法，FISH可提供额外信息； CGH 是最不敏感的方法。除了两名 FA 患者的 7 号单体异常外，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 患者已发展为形态学 MDS。在 5 名 FA 患者中，有 3 名患者出现临床显着的 MDS 之前出现异常克隆。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，以确定单独的细胞遗传学以及结合骨髓形态和临床评估在这些罕见疾病中的预后意义。