EPIDEMIOLOGY, TREATMENT, BIOLOGY OF JUVENILE MYELOGENOUS LEUKEMIA & MONOSOMY 7

这项转化研究提案涉及流行病学，生物学 和治疗患有相关白血病前期疾病的儿童 慢性粒细胞白血病和骨髓单体7综合征 (JCML/Mo7）。这些疾病共有许多主要的临床特征， 表明它们在致病上相关;然而， 他们之间是不确定的。JCML/Mo 7儿童的治疗结果 即使是同种异体骨髓移植也是令人沮丧的。这 这项建议是基于最近的流行病学调查结果， 产科和父母的职业危险因素与发展 婴儿期的骨髓性白血病;观察到一些儿童 与JCML显示临床反应分化剂顺式 视黄酸;以及分子遗传学和生物化学研究， 暗示通过p21 ras蛋白家族的信号失调， 这些恶性骨髓疾病的发病机制。我们将测试 假设JCML/Mo 7与遗传和获得性风险相关 与特定分子和细胞遗传学相关的因素 患者骨髓的改变，这些分子标记物将 具有预后价值，并可用于衡量治疗反应。

This translational research proposal addresses the epidemiology, biology and treatment of children with the related preleukemic conditions juvenile chronic myelogenous leukemia and bone marrow monosomy 7 syndrome (JCML/Mo7). These disorders share a number of major clinical features that suggest they are related pathogenically; however, the precise relationship between them is uncertain. Treatment results in children with JCML/Mo7 have been dismal even with allogeneic bone marrow transplantation. This proposal is based upon recent epidemiological findings linking specific obstetric and parental occupational risk factors with the development of myeloid leukemia during infancy; upon the observation that some children with JCML have show clinical responses to the differentiating agent cis retinoic acid; and upon molecular genetic and biochemical studies that implicate deregulated signaling through the p21 ras family of proteins in the pathogenesis of these malignant myeloid disorders. We will test the hypothesis that JCML/Mo7 are associated with genetic and acquired risk factors which correlate with specific molecular and cytogenetic alterations in patient bone marrows, and that these molecular markers will be of prognostic value and can be used to measure responses to treatment.