Twenty-first Annual Fanconi Anemia Research Fund Scientific Symposium

简介（申请人提供）：第21届范可尼贫血研究基金科学研讨会。范可尼贫血（FA）是一种罕见的遗传性疾病，其特征是骨髓衰竭、发育异常、骨髓增生异常（MDS）、急性非淋巴细胞白血病（AML）、实体瘤和细胞对交联剂过敏。范可尼贫血的一个独特特征是在生命早期发生特异性上皮和造血恶性肿瘤，通常只在老年人群中发现。这些蛋白质的功能在很大程度上是未知的，但它们彼此形成复合物，在一个典型的“途径”中，11种已知的范可尼贫血蛋白中的8种结合在一起，形成一个复合物和单泛素化的FANCD2，其中一种蛋白质不在“核心”复合物中。有体外和体内的证据表明，至少有一些FA蛋白还通过与信号分子形成复合物来促进造血细胞的存活信号通路。干细胞移植是符合条件的骨髓衰竭患者的治疗选择。骨髓衰竭的幸存者最终面临发展成鳞状细胞癌的极高风险。这种疾病是基因治疗的理想候选者，因为补充干细胞固有的选择性。越来越多的证据表明，FA信号通路的功能障碍可以随着非fanconi患者肿瘤细胞的体细胞变化（表观遗传和遗传）而发展，这种体细胞变化的后果抑制了自我复制的潜力，并增强了祖细胞池的衰老。

DESCRIPTION (provided by applicant): Twenty-first Annual Fanconi Anemia Research Fund Scientific Symposium. Fanconi anemia (FA) is a rare hereditary disease characterized by bone marrow failure, developmental anomalies, a high incidence of myelodysplasia (MDS), acute non-lymphocytic leukemia (AML), solid tumors, and cellular hypersensitivity to cross-linking agents. A unique feature of Fanconi anemia is the development, in early life, of specific epithelial and hematopoietic malignancies usually found only in aging populations. 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 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. Survivors of bone marrow failure ultimately face an extremely high risk of developing squamous cell cancers. The disease is an ideal candidate for gene therapy because of the inherent selectability of complemented stem cells. Broad evidence is being developed that dysfunction of the FA signaling pathways can develop as somatic changes (epigenetic and genetic) in neoplastic cells arising in non-Fanconi patients and that the consequences of such somatic changes suppress self-replicative potential and enhance senescence in progenitor cell pools. The Annual Fanconi Anemia Research Fund Scientific Symposium brings together investigators from around the world to discuss all basic, translational, and clinical research aspects of this rare disease. The meeting provides a unique opportunity for investigators to cross-fertilize and to develop interdisciplinary research projects. Not only will the data be shared freely with all investigators, the files will be made accessible through GeneSifter, an online bio-information tool. This application seeks partial support for this meeting, scheduled to be held in Baltimore, Maryland in October 2009. PUBLIC HEALTH RELEVANCE: Twenty-first Annual Fanconi Anemia Research Fund Scientific Symposium. The Fanconi Anemia Research Fund's Annual Symposia are the only scientific conferences convened that focus on Fanconi anemia (FA). Recent research has established the importance of Fanconi anemia genes in tumor suppression, DNA repair, stem cell function, and suppression of apoptosis and senescence; thus, advances made in FA science have an impact beyond affected patients and families. Acquired abnormalities of FA genes and FA gene expression have been reported in patients with sporadic malignancies of plasma cells, leukemia, head and neck cancer, lung cancer, and ovarian cancer.