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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.

这个项目涉及白血病集落形成细胞的研究

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。