CHARACTERIZATION OF ACUTE MYELOGENOUS LEUKEMIA STEM CELL

急性髓性白血病干细胞的表征

基本信息

批准号：
3446987
负责人：
ALEXANDRA L HOWELL
金额：
$ 5.26万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-07-01 至 1990-03-31
项目状态：
已结题

项目摘要

This project involves the study of the leukemia-colony forming cell population (L-CFC) in patients with acute myelogenous leukemia (AML). In one aspect of this study, the cell surface antigens expressed by the L-CFC will be examined in patients with AML using a panel of myeloid-specific monoclonal antibodies and complement-mediated cytotoxicity. Patients will be examined serially on subsequent relapses to determine whether the L-CFC phenotype is stable with time. The findings from these studies will then be compared to a series of experiments designed to examine the inducibility to maturation of the L-CFC using various agents known to effect myeloid cell differentiation. The agents to be tested include recombinant gamma interferon, 1,25 dihydroxyvitamin D3, and cis-retinoic acid. Changes in surface antigens, proliferative potential, and morphology will be examined in the L-CFC exposed to optimal concentrations of the maturation-inducing agents. The studies are designed to examine whether the L-CFC in AML is responsive to agents of differentiation, and to determine whether response is manifested in cellular changes similar to those of normal myelopoiesis (i.e., expression of a more differentiated cell phenotype and a reduction in cellular proliferation). Another aspect is to correlate the cell surface antigenic display of both normal and leukemic myeloid cells with oncogene expression. The expression of three myeloid-associated cellular oncogenes (c-onc) will be studied: N-ras, c-myc and c-fos. Oncogene expression will be quantified by hybridization of probes to c-onc RNA extracted from normal myeloid subpopulations (monocytes and neutrophils) and from leukemia blast cell populations from patients with AML. Expression of oncogene protein products will be determined by immunofluorescence studies using antisera to the oncogene proteins, and by immunoprecipitation studies of radiolabelled cell lysates. The aim of these studies is to correlate the expression of oncogenes with patterns of myeloid cell-surface antigens on normal and malignant cells to determine whether there is a relationship with differentiation status. Results will further our understanding of leukemia cell biology in AML, and are directed towards clarifying the maturational defect that occurs in myelogenous leukemia. By determining the maturational capabilities of the L-CFC population, alternative approaches to therapy, including immunotherapy and maturation-inducing therapy, may result.

该项目涉及白血病集落形成细胞的研究急性髓性白血病（AML）患者人群（L-CFC）。在本研究的一方面，L-CFC 表达的细胞表面抗原将使用一组骨髓特异性试剂盒对 AML 患者进行检查单克隆抗体和补体介导的细胞毒性。患者会在随后的复发中进行连续检查，以确定 L-CFC 是否表型随时间稳定。这些研究的结果随后将与旨在检查诱导性的一系列实验进行比较使用已知影响骨髓的各种试剂促进 L-CFC 的成熟细胞分化。待测试的试剂包括重组γ 干扰素、1,25二羟基维生素D3和顺式视黄酸。变化将检查表面抗原、增殖潜力和形态在暴露于最佳浓度的成熟诱导剂的 L-CFC 中代理。这些研究旨在检验 AML 中的 L-CFC 是否对分化剂有反应，并确定是否有反应表现为与正常骨髓细胞生成相似的细胞变化（即，更加分化的细胞表型的表达和减少细胞增殖）。另一方面是将两者的细胞表面抗原展示相关联具有癌基因表达的正常和白血病骨髓细胞。表达式将研究三种骨髓相关细胞癌基因 (c-onc)： N-ras、c-myc 和 c-fos。癌基因表达将通过以下方式量化探针与从正常骨髓中提取的 c-onc RNA 杂交亚群（单核细胞和中性粒细胞）和白血病母细胞来自 AML 患者的人群。癌基因蛋白的表达产品将通过使用抗血清的免疫荧光研究来确定癌基因蛋白，并通过放射性标记的免疫沉淀研究细胞裂解物。这些研究的目的是关联表达正常和正常细胞上具有髓样细胞表面抗原模式的癌基因以确定是否与恶性细胞有关系分化状态。结果将进一步加深我们对白血病的了解 AML 中的细胞生物学，旨在阐明成熟细胞骨髓性白血病中发生的缺陷。通过确定左旋氟氯化碳群体的成熟能力，替代方法治疗，包括免疫疗法和成熟诱导疗法，可能结果。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Monoclonal antibodies to carbohydrate antigens in autologous bone marrow transplantation.

自体骨髓移植中针对碳水化合物抗原的单克隆抗体。

DOI：
10.1002/jcb.240360412
发表时间：
1988
期刊：
Journal of cellular biochemistry
影响因子：
4
作者：
Ball,ED;Howell,AL
通讯作者：
Howell,AL

Distribution of the 124-kd antigen defined by monoclonal antibody AML-1-99 on normal and leukemic myeloid cells.

单克隆抗体 AML-1-99 定义的 124-kd 抗原在正常和白血病骨髓细胞上的分布。

DOI：
发表时间：
1988
期刊：
Experimental hematology
影响因子：
2.6
作者：
Howell,AL;Miller,R;Keefe,KA;McIntyre,OR;Stockner,M;Sullivan,R;Hibbert,SR;Noelle,RJ;Ball,ED
通讯作者：
Ball,ED

Induction of differentiation in blast cells and leukemia colony-forming cells from patients with acute myeloid leukemia.

急性髓性白血病患者的母细胞和白血病集落形成细胞的分化诱导。