SECONDARY HEMATOLOGIC DISORDERS--GENESIS AND TREATMENT

继发性血液病——起源和治疗

• 批准号: 2406364
• 负责人: HARVEY D PREISLER
• 金额: $ 187.88万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-08 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2406364
• 关键词: acute lymphocytic leukemia; blood /lymphatic neoplasm; blood disorder; carcinogenesis; neoplasm /cancer genetics; preneoplastic state

One of the major challenges facing the field of Hematology and Oncology is that of the secondary hematologic disorders. These disorders are becoming increasingly common, at least in part because of the effectiveness of high dose cytotoxic therapy in the treatment of patients with malignant disease. As many as 10% of patients cured of malignant disease by therapy with DNA damaging agents will develop a hematologic disorder and this percentage may be double in patients who are treated with autologous stem cell transplantation as part of their curative therapy. The rapid clinical course of both secondary MDS and secondary AML makes the development of these disorders in patients already cured of one malignancy especially disturbing. While a great deal of information is available regarding a variety of molecular genetic abnormalities which have been detected in MDS and AML, little or no information is available with respect to how often multiple genetic abnormalities are present and little information is available regarding the biological consequences of these abnormalities. The lack of information in these areas severely restricts our understanding of the development of MDS and AML. The studies which will be conducted as part of this Program Project will focus on the most common molecular genetic lesions of these disorders, will study these lesions simultaneously in the same patients, the in vivo and in vitro biological characteristics of the abnormal cells will be identified and related to the genetic lesions which are present. Parallel in vitro studies will help to define the mechanisms underlying these associations. Special emphasis will be placed in two areas: 1 - on MDS and AML characterized by deletions of chromosomes 5 and/or 7 q and 2 - on aberrant cytokine production in these diseases and the role which it plays in the genesis of both MDS and AML. These two areas of particular interest, the former because the stability of these genetic lesions as the disease evolves from MDS to AML strongly suggests a key role of these lesions in the genesis of these disorders and the second because of our demonstrated ability to suppress abnormal cytokine production in vivo in patients and thus alter the behavior of both MDS and AML cells. This later ability offers the prospect of rapidly applying the results of the laboratory studies to the clinic to improve treatment outcome in both MDS and AML.

血液学领域面临的主要挑战之一， 肿瘤是继发性血液系统疾病。这些 疾病变得越来越普遍，至少部分原因是 高剂量细胞毒疗法在治疗 恶性疾病患者。 多达10%的患者治愈 用DNA损伤剂治疗的恶性疾病将发展 血液系统疾病，这一比例可能会增加一倍， 自体干细胞移植治疗的患者， 他们的治疗方法 快速的临床过程， MDS和继发性AML使这些疾病的发展 在已经治愈了一种恶性肿瘤的患者中尤其令人不安。 虽然有大量的信息是关于各种 在MDS中检测到的分子遗传异常， AML，很少或根本没有关于发生频率的信息 存在多种遗传异常， 关于这些异常的生物学后果。 这些领域信息的缺乏严重限制了我们的 了解MDS和AML的发展。 研究 将作为本计划项目的一部分进行，重点是 这些疾病中最常见的分子遗传病变， 在相同的患者中同时研究这些病变， 异常细胞的体外生物学特性将被 确定并与存在的遗传病变相关。 平行 体外研究将有助于确定这些潜在的机制， 协会. 将特别强调两个方面： 以5号和/或7号染色体缺失为特征的MDS和AML q和2 -对这些疾病中异常细胞因子产生的影响， 它在MDS和AML的发生中发挥的作用。 这两 特别感兴趣的领域，因为前者的稳定性，这些 随着疾病从MDS发展到AML， 表明这些病变在这些疾病的发生中起着关键作用 第二是因为我们已经证明了 在患者体内产生异常的细胞因子，从而改变 MDS和AML细胞的行为。这种能力提供了 前景将实验室研究结果应用于 改善MDS和AML的治疗结果。