24th Annual Fanconi Anemia Research Fund Scientific Symposium

描述（由申请人提供）：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）高发、急性非淋巴细胞白血病（AML）、实体瘤和细胞对交联剂过敏。范可尼贫血的独特特征是骨髓衰竭的发展几乎是普遍的，并且在早期发展为特异性上皮和造血恶性肿瘤的相对风险很高，通常只在老年人群中发现。对成年FA患者的评估显示鳞状细胞癌（SCC）的发病率惊人且不祥，尤其是头颈部和妇科。此外，FA患者体细胞的遗传不稳定性意味着暴露于电离辐射、环境致癌物和化疗药物对患者构成独特的风险。这些蛋白的具体生化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，已知的15种范可尼贫血蛋白中的8种结合在一个复合物中，促进FANCD2的单泛素化。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。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导致FA患者肿瘤细胞的体细胞改变（表观遗传和遗传），获得性FA蛋白功能障碍也可发生在非fanconi患者的遗传和表观遗传上。第24届范可尼贫血研究基金科学研讨会将于2012年9月27日至30日在科罗拉多州丹佛市举行。为期三天的会议将由受邀的主题演讲者和大约45个单轨格式的口头摘要报告组成。大约55个额外的摘要将被选择用于海报展示。研讨会汇集了来自世界各地的主要研究人员和医生以及年轻研究人员，讨论这种罕见疾病的基础科学、转化和临床研究方面的问题。不收取注册费，部分原因是为了鼓励学生和年轻研究者的参与。会议为研究人员提供了一个独特的机会来交叉施肥和发展跨学科的研究项目。本申请寻求部分支持演讲者和主要人员出席这一重要会议的国内旅费。

DESCRIPTION (provided by applicant): Fanconi anemia (FA) is a rare hereditary disease characterized by bone marrow failure, developmental anomalies, high incidence of myelodysplasia (MDS), acute non-lymphocytic leukemia (AML), solid tumors, and cellular hypersensitivity to cross-linking agents. Unique features of Fanconi anemia are the nearly universal development of bone marrow failure and a high relative risk of developing, at an early age, specific epithelial and hematopoietic malignancies usually found only in aging populations. Evaluation of adult FA patients reveals a striking and ominous incidence of squamous cell carcinomas (SCC), especially of the head and neck and gynecological tract. Moreover, the genetic instability of the somatic cells in the FA patient means that exposure to ionizing radiation, environmental carcinogens and chemotherapeutic agents pose unique risks to the patient. The specific biochemical functions of the proteins is largely unknown, but many form complexes with each other and in one canonical pathway, eight of the fifteen known Fanconi anemia proteins bind together in a complex and facilitate the monoubiquitination of FANCD2. There is in vitro and in vivo evidence suggesting 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. 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 result in somatic changes (epigenetic and genetic) in neoplastic cells arising in FA patients and that acquired FA protein dysfunction can also occur genetically and epigenetically in non-Fanconi patients. The 24th Annual Fanconi Anemia Research Fund Scientific Symposium will be held in Denver, CO, Sept. 27-30, 2012. The three-day conference will be comprised of invited keynote speakers and approximately 45 oral abstract presentations in a single-track format. Approximately 55 additional abstracts will be selected for poster presentations. The Symposium brings together leading researchers and physicians as well as young investigators from around the world to discuss basic science, translational, and clinical research aspects of this rare disease. No registration fee is charged, n part to encourage participation of students and young investigators. The meeting provides a unique opportunity for investigators to cross-fertilize and develop interdisciplinary research projects. This application seeks partial support for domestic travel costs for speakers and key personnel to attend this important conference. PUBLIC HEALTH RELEVANCE: The annual Fanconi Anemia Research Fund Scientific Symposium is the only major scientific conference convened to focus exclusively 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 patients and families affected by this rare disease. 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.