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。分析包括经过集中评论的骨髓形态，G带核型分析，荧光原位杂交（FISH）和比较基因组杂交（CGH）。患者最多跟踪了五年。在FA患者中有6例（46％）患者中有6例（46％）患者，有14例DBA患者，四名（50％）患有SDS的患者中有14例（46％）患者中有6例（46％）患者中的6例（46％）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。除了两名FA患者中的7个单肌除外，异常类型与从头MDS患者常见的异常类型不同。一名具有正常骨髓核型的FA患者已经形成了形态学MD。在FA的五名患者中，三名异常克隆先于临床上具有显着的MDS。此外，在两名FA患者中，异常的克隆在大小上蜡和减弱，甚至消失了。这些初步数据表明，IBMFS患者的骨髓核型异常可能与其他从头MDS患者有所不同，并支持对仅细胞遗传学的大型协作数据库的需求，以便在这些稀有的稀有分歧中确定细胞遗传学的意义，并与骨髓形态和临床评估相结合。