Eighteenth Annual Fanconi Anemia Research Symposium

描述（由申请人提供）： 范可尼贫血是一种罕见的遗传性疾病，其特征在于骨髓衰竭、发育异常、骨髓增生异常（MDS）、急性非淋巴细胞白血病（AML）和实体瘤的高发病率以及对交联剂的细胞超敏反应。这些蛋白质的功能在很大程度上是未知的，但许多蛋白质彼此形成复合物，并且在一个典型的“途径”中，11种已知的范可尼贫血（FA）蛋白质中的8种以复合物和单泛素FANCD 2结合在一起，FANCD 2是不在核心复合物中的蛋白质之一。 有体外和体内证据表明，至少一些FA蛋白也通过与信号分子形成复合物来促进造血细胞中的存活信号通路。 干细胞移植是符合条件的骨髓衰竭患者的治疗选择，许多骨髓衰竭的幸存者会发展成鳞状细胞癌。 这种疾病是基因治疗的理想候选者（因为补充干细胞的固有选择性）。广泛的证据正在开发，以及功能障碍的FA信号通路可以发展为体细胞的变化（表观遗传和遗传）在肿瘤细胞中出现在非范可尼患者。范可尼贫血研究基金每年为研究人员提供赠款支持，家庭支持，家庭务虚会，特别共识会议和出席人数众多的国际范可尼贫血研究研讨会。这个年度研讨会汇集了来自世界各地的研究人员，讨论这种疾病的所有基础，转化和临床研究方面。会议为研究人员提供了一个独特的机会，以交叉施肥和开发跨学科的研究项目。其中一个即将完成的项目是国际范科尼贫血转录组联盟，其最终结果将在2006年10月的会议上公布，该项目最初由FA研究基金资助，随后得到NHLBI微阵列中心的资助。这些数据不仅将与所有研究人员免费共享，而且任何人都可以通过GeneSifter访问这些文件，GeneSifter是一种在线生物信息学工具，可用于在线分析。本申请寻求对定于2006年10月在贝塞斯达举行的这次会议的部分支持。

DESCRIPTION (provided by applicant): Fanconi anemia is a rare hereditary disease characterized by bone marrow failure, developmental anomalies, a high incidence of myelodysplasia (MDS), acute non-lymphocytic leukemia (AML), and solid tumors, and cellular hypersensitivity to cross-linking agents. The function of the proteins is largely unknown but many form complexes with each other and in one canonical "pathway" eight of the eleven known Fanconi anemia (FA) proteins bind together in a complex and monoubiquitinate FANCD2, one of the proteins not in the core complex. There is in vitro and in vivo evidence that at least some of the FA proteins also promote survival signaling pathways in hematopoietic cells by forming complexes with signaling molecules. Stem cell transplantation is the treatment of choice for eligible patients with bone marrow failure and squamous cell cancers develop in many of the survivors of bone marrow failure. The disease is an ideal candidate (because of the inherent selectability of complemented stem cells) for gene therapy. Broad evidence is being developed as well that dysfunction of the FA signaling pathways can develop as somatic changes (epigenetic and genetic) in neoplastic cells arising in non-Fanconi patients. Each year the Fanconi Anemia Research fund provides grant support for investigators, family support, family retreats, special consensus conferences, and a well-attended international Fanconi anemia research symposium. This annual symposium brings together investigators from around the world to discuss all basic, translational, and clinical research aspects of this disease. The meeting provides a unique opportunity for investigators to cross-fertilize and to develop interdisciplinary research projects. One nearing completion, funded initially by the FA Research Fund and subsequently through the NHLBI Microarray Center grant support, is the International Fanconi Anemia Transcriptome Consortium, final results of which will be presented at the October 2006 meeting. Not only will the data be shared freely with all investigators, the files will be made accessible to anyone through GeneSifter, an online bioinformatics tool that can be used from on-line analysis. This application seeks partial support for this meeting, scheduled to be held in Bethesda in October 2006.