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.

遗传性的骨髓衰竭综合征（IBMF）是一群具有独特表型和实验室异常的稀有遗传疾病的异质群。 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). 为了确定IBMF患者中异常骨髓核型的发生率，类型和可能的临床意义，我们正在进行骨髓的前瞻性，连续性，常规，常规和分子细胞遗传学分析。 我们假设异常的骨髓核型，没有其他MDS的证据（明显的细胞质或形态呼吸障碍）可能无法预测不良结果。分析包括中央回顾的骨髓形态，G带核型分析，荧光原位杂交（FISH），比较基因组杂交（CGH）和光谱核分型（SKY）。 患者已遵循多达9年。 在FA患者中有9例（47％）患者中有9名（47％）患者中有9例（47％）患者，患有DBA的患者中有9名（60％（60％）患有SDS的患者中有3例（47％）患者中有9例（47％）患者，有27例（11％）患者中有3例（11％（11％）患者中，有26名（0％）患者中，已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提供了其他信息。 CGH是最不灵敏的方法。在我们的IBMF患者中，约有一半的克隆异常与偶发的MDS或AML患者常见的患者不同。 在临床上稳定且没有形态MD的IBMFS患者中发现了异常克隆。 此外，这些克隆中的一些随着时间的流逝而逐渐减弱。 这些数据表明，IBMF中细胞遗传学变化的临床或可能是生物学的意义可能与其他从头骨髓衰竭或MDS的患者不同。我们目前正在完成并验证我们的临床，细胞遗传学和骨髓形态数据库，以准备进行横截面和纵向分析，并在这一独特的患者队列中发布发现。