Novel Hematopoietic Factors Produced by Human Undifferentiated Leukemia Cell Lines. and Their Biological Significance

人类未分化白血病细胞系产生的新型造血因子。

• 批准号: 03404067
• 负责人: ASANO Shigetaka
• 金额: $ 12.8万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03404067/
• 关键词: Undifferentiated Leukemia Cell Line; MB-1; Hematopoietic Factor; Cytokine; Mast cell; Hematopoietic Stem Cell; SCID mouse; cDNA Cloning; cDNAライブラリー; 精製; ヌードマウス; 白血病細胞株; SCF; ストローマ細胞; 慢性骨髄性白血病; ヌ-ドマウス; 骨髄芽球; 造血前駆細胞; ストロ-マ細胞; 細胞相互作用

The MB-1 cell line, which was derived from the blastoma of a patient with chronic myelogenous leukemia (CML), is transplantable to nude mice. Mast cell growth-stimulating activity was detected in the culture supernatant of TPA-treated MB-1 cells. Since it is possible that cytokines which stimulate the growth of mast cells have the ability to act on hematopoietic stem cells, it is worth while characterizing the MB-1-derived activity. Although the purification and cDNA cloning of the mast cell growth-stimulating activity of MB-1 cells are still ongoing, our preliminary results suggested that this may be a novel cytokine with a unique activity on mast cells.We also attempted to establish human leukemia cell lines. The IMS-M1, a monoblastic leukemia cell line with t(9 ; 11) translocation, was established using an in vitro culture system. Unexpectedly, most leukemia samples ware not transplntable to SCID mice, probably due to the absence of appropriate human hematopoietic growth factors.The other research subjects include malignant transformation of myloid cells using a gene transfer technique and their characterization, molecular cloning of G-CSF-induced gene cDNA, analysis of hematopoiesis-supporting ability of a differentiation-inducible mouse embryo fibroblast cell line (C3H10T1/2), construction of cDNA library derived from human fetal liver, and so forth.

MB-1细胞系源自慢性粒细胞白血病（CML）患者的母细胞瘤，可移植到裸鼠体内。在 TPA 处理的 MB-1 细胞的培养上清液中检测到肥大细胞生长刺激活性。由于刺激肥大细胞生长的细胞因子可能具有作用于造血干细胞的能力，因此值得表征 MB-1 衍生的活性。尽管MB-1细胞的肥大细胞生长刺激活性的纯化和cDNA克隆仍在进行中，但我们的初步结果表明这可能是一种对肥大细胞具有独特活性的新型细胞因子。我们还尝试建立人白血病细胞系。 IMS-M1 是一种具有 t(9 ; 11) 易位的单核细胞白血病细胞系，是使用体外培养系统建立的。出乎意料的是，大多数白血病样本无法移植到 SCID 小鼠中，可能是由于缺乏适当的人类造血生长因子。其他研究课题包括利用基因转移技术进行髓样细胞的恶性转化及其表征、G-CSF诱导基因 cDNA 的分子克隆、分化诱导小鼠胚胎的造血支持能力分析 成纤维细胞系（C3H10T1/2）、人胎肝cDNA文库的构建等。

项目成果

Uemura, N.: "Acquisition of IL-3-independence in FDC-P2 cells after transfection with the activated c-H-ras gene using a bovine papillomavirus plamid vector." Blood. 80. 3198-3204 (1992)

Uemura, N.：“使用牛乳头瘤病毒质粒载体转染激活的 c-H-ras 基因后，FDC-P2 细胞获得 IL-3 独立性。”

K.Tani et al: "Implantation of genetically manipulated fibroblasts into mice as a model of cytokine supplementation gene therapy using human GーCSF and IFNーalpha cDNAs." Molecular Approaches to the Study and Treatment of Human Diseases.

K. Tani 等人：“将基因工程成纤维细胞植入小鼠体内，作为使用人类 G-CSF 和 IFN-α cDNA 进行细胞因子补充基因治疗的模型。”

Yoshikubo, T.: "Adhesion of NFS-60 myeloid leukemia cells to MC3T3-G2/PA6 stromal cells induces G-CSF production" Blood. (in press).

Yoshikubo, T.：“NFS-60 髓系白血病细胞与 MC3T3-G2/PA6 基质细胞的粘附诱导 G-CSF 产生”血液。

Uemura,N.,Asano,S.,et al.: "Binding of membrane-anchored macrophage colony-stimulating factor(M-CSF)to its receptor mediates specific adhesion between stromal cells and M-CSF-receptor-bearing hematopoietic cells." Blood. 88. 2634-2640 (1993)

Uemura,N.、Asano,S.等人：“膜锚定巨噬细胞集落刺激因子 (M-CSF) 与其受体的结合介导基质细胞与带有 M-CSF 受体的造血细胞之间的特异性粘附。

Takahashi,S.,et al.: "Recombinant human glycosylated granulocyte colony-stimulating factor(rhG-CSF)-combined regimen for a allogeneic bone marrow transplantation in refractory acute myeloid leukemia." Bone Marrow Transplant. (in press).

Takahashi,S.,et al.：“重组人糖基化粒细胞集落刺激因子 (rhG-CSF) 联合方案用于难治性急性髓性白血病的同种异体骨髓移植。”