Significance of Marrow Karyotypes in Inherited Bone Marrow Failure Syndromes

骨髓核型在遗传性骨髓衰竭综合征中的意义

• 批准号: 8552778
• 负责人: diane c arthur
• 金额: $ 10.3万
• 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/8552778
• 关键词: Acute Myelocytic Leukemia; Aplastic Anemia; Biological; Bone Marrow; Chromosome abnormality; Clinical; Cytogenetic Analysis; Cytogenetics; Data; Databases; Detection; Diamond; Diamond-Blackfan anemia; Disease; Dyskeratosis Congenita; Dysmyelopoietic Syndromes; Fanconi' s Anemia; Fluorescent in Situ Hybridization; G-Banding; Hereditary Disease; Incidence; Inherited; Karyotype; Laboratories; Marrow; Methods; Molecular Cytogenetics; Morphology; Pancytopenia; Patients; Preparation; Publishing; Risk; Running; Spectral Karyotyping; Syndrome; Technology; Testing; Time; Waxes; adverse outcome; clinically significant; cohort; comparative genomic hybridization; cytopenia; prospective; response

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), comparative genomic hybridization (CGH) and spectral karyotyping (SKY). Patients have been followed for up to nine years. Clonal chromosome abnormalities have been detected in nine of 19 (47 percent) patients with FA, none of 26 (0 percent) patients with DBA, three of five (60 percent) patients with SDS, and three of 27 (11 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. Approximately half of the clonal abnormalities documented among our patients with IBMFS are different from those commonly found in patients with sporadic MDS or AML. Abnormal clones have been found in IBMFS patients who are clinically stable and do not have morphologic MDS. Furthermore, some of these clones have waxed and waned over time. These data suggest the clinical, and possibly biological, significance of cytogenetic changes in IBMFS may be different from other patients with de novo bone marrow failure or MDS. We are currently completing and verifying our clinical, cytogenetic, and marrow morphology databases in preparation for running cross-sectional and longitudinal analyses and publishing the findings in this unique cohort of patients.

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)、比较基因组杂交 (CGH) 和光谱核型分析 (SKY)。 患者已被随访长达九年。 19 名 FA 患者中的 9 名（47%）检测到克隆染色体异常，26 名 DBA 患者中没有检测到克隆染色体异常（0%），5 名 SDS 患者中检测到 3 名（60%），27 名 DC 患者中检测到 3 名（11%）。 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。我们的 IBMFS 患者中记录的克隆异常中大约有一半与散发性 MDS 或 AML 患者中常见的克隆异常不同。 在临床稳定且没有形态学 MDS 的 IBMFS 患者中发现了异常克隆。 此外，其中一些克隆随着时间的推移而盛衰。 这些数据表明，IBMFS 细胞遗传学变化的临床意义（可能还有生物学意义）可能与其他新发骨髓衰竭或 MDS 患者不同。我们目前正在完成和验证我们的临床、细胞遗传学和骨髓形态数据库，为运行横断面和纵向分析并发布这一独特患者队列的研究结果做准备。