Significance of Marrow Karyotypes in Inherited Bone Marrow Failure Syndromes

遗传性骨髓衰竭综合征（IBMFS）是一组异质性的罕见疾病， 具有独特的表型和实验室异常的遗传性疾病。患者 IBMFS，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）的患者发生再生障碍的风险增加 贫血（AA）、骨髓增生异常综合征（MDS）和急性髓性白血病（AML）。以确定 骨髓异常核型的发生率、类型和可能的临床意义 在IBMFS患者中，我们正在进行前瞻性、系列、常规和分子生物学研究， 骨髓细胞遗传学分析。我们假设骨髓核型异常， MDS的证据（显著的血细胞减少或形态学发育不良），可能不能预测不良反应。 结果。分析包括集中审查的骨髓形态学、G带核型 荧光原位杂交（FISH）和比较基因组杂交 （CGH）。患者已随访长达8年。克隆染色体异常 16例FA患者中有6例（38%）检测到，21例（0%） DBA，5例SDS患者中的3例（60%），20例DC患者中的2例（10%）。 G显带是检测异常克隆的最佳方法，FISH提供了额外的 CGH是最不敏感的方法。大约一半的克隆异常 在我们的IBMFS患者中记录的与在患者中常见的不同， 散发性骨髓增生异常综合征或急性粒细胞白血病在临床上表现为IBMFS的患者中发现了异常克隆 稳定且没有形态学MDS。此外，这些克隆中的一些已经出现了盛衰 随着时间这些数据表明，可能需要更保守的治疗方法， 已知对细胞毒性化疗和放疗敏感的IBMFS患者。到 确定骨髓核型异常的预后和生物学意义， IBMFS患者，包括形态学和临床数据的大型协作数据库， needed.

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 eight years. Clonal chromosome abnormalities have been detected in six of 16 (38 percent) patients with FA, none of 21 (0 percent) patients with DBA, three of 5 (60 percent) patients with SDS, and two of 20 (10 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 a more conservative approach to therapy may be indicated in IBMFS patients who are known to be sensitive to cytotoxic chemotherapy and radiotherapy. To determine the prognostic and biological significance of abnormal bone marrow karyotypes in IBMFS patients, large collaborative databases including morphologic and clinical data are needed.