Genetic and molecular studies on the oncogenesis of hematopoietic malignancies

造血系统恶性肿瘤发生的遗传学和分子研究

• 批准号: 01480301
• 负责人: TAKATSUKI Kiyoshi
• 金额: $ 4.1万
• 依托单位: KUMAMOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480301/
• 关键词: Oncogene; Adult T-Cell Leukemia; Multiple myeloma; Chromosome; Cell line; Cytokine; Immunoglobulin; T-cell receptor; 造血器腫瘍; 成人T細胞白血病(ATL); B細胞腫瘍; 発癌機構; レトロウィルス; 癌抑制遺伝子; 白血病; 免疫グロブリン遺伝子; T細胞受容体遺伝子; 染色体異常; GーCSF; Nーras; 骨髄性白血病; LD78遺伝子

We tried to clarify the oncogenesis of hematopoietic maliganancies, especially lymphocytic maliganancies such as adult T-cell leukemia (ATL) and multiple myeloma. We also tried to establish the cell line from the patients with chromosome abnormalities.1) We established amylase-producing myeloma cell line (KHM-1) from a patient with hyperamyalasemia. Chromosome analysis showed a translocation between near the amylase gene locus and the abl oncogene locus. This cell line operates under an autocrine growth mechanism with respect of these two cytokines, IL-6 and TNF-alpha.2) The cell line (KHM-2B) expressing two oncogene products, c-myc and bcl-2, was established from a patient with acute lymphocytic leukemia with an 8 ; 14 and 14 ; 18 chromosome translocation. In this cell line, two oncogenes were activated by two translocations to immunoglobulin genes.3) We studied the rearrangement and expression of the immunoglobulin (Ig) and T-cell receptor (TCR) genes in 12 patients with acute unclassified leukemia (AUL). Our results suggest that AUL may generally originate from undifferentiated cells with an aberrant rearrangement and/or expression of the Ig and TCR genes.4) We showed that p53 tumor suppressor gene was frequently mutated in the acute phase of ATL. These results suggests that p53 mutations may be associated with the transition from chronic to acute ATL. On the other hand, cell surface expression of the TCR/CD3 complex were very low on the cells from acute type ATL, but not from chronic type ATL.

我们试图阐明恶性血液病的致癌机制，特别是淋巴细胞性恶性疾病，如成人T细胞白血病(ATL)和多发性骨髓瘤。我们还尝试建立了染色体异常患者的细胞系1)我们从一名高淀粉酶血症患者建立了产生淀粉酶的骨髓瘤细胞系(KHM-1)。染色体分析显示淀粉酶基因座与ABL癌基因座之间存在易位。2)表达c-myc和bcl2两种癌基因产物的细胞系(KHM-2B)是从一例8；14和14；18染色体易位的急性淋巴细胞白血病患者身上建立的。3)我们研究了12例急性未分型白血病(AUL)患者免疫球蛋白(Ig)和T细胞受体(TCR)基因的重排和表达。我们的结果提示AUL一般可能起源于Ig和TCR基因异常重排和/或表达的未分化细胞。4)我们发现P53抑癌基因在ATL急性期经常发生突变。这些结果提示P53基因突变可能与ATL从慢性向急性转化有关。TCR/CD3复合体在急性型ATL细胞表面表达很低，而在慢性型ATL细胞表面表达不明显。

项目成果

Hiromitsu Matsuzaki: "Establishment and characterization of acute Bーcell Iymphocytic leukemia cell line showing (8;14) and (14;18) chromosome translocation" Acta Haematologica. 84. 156-161 (1990)

Hiromitsu Matsuzaki：“显示 (8;14) 和 (14;18) 染色体易位的急性 B 细胞淋巴细胞系的建立和表征”Acta Haematologica。84. 156-161 (1990)。

Norio Asou,Toshio Hattori,Kiyoshi Takatsuki他2名: "Rearrangements of T-cell antigen receptor δ chain gene in hematologic neoplasms" Blood. 74. 2707-2712 (1989)

Norio Asou、Toshio Hattori、Kiyoshi Takatsuki 和另外 2 人：“血液肿瘤中 T 细胞抗原受体 δ 链基因的重排”《血液》74. 2707-2712 (1989)。

HIROYUKI HATA: "Autocrine growth by two cytokines,interleukin-6 and tumor necrosis factor alpha,in the myeloma cell line KHM-1A" Acta Haematol.83. 133-136 (1990)

HIROYUKI HATA：“骨髓瘤细胞系 KHM-1A 中两种细胞因子白细胞介素 6 和肿瘤坏死因子 α 的自分泌生长”Acta Haematol.83。

AKIKO SAKASHITA: "Mutation of the p53 gene in adult T-cell leukemia" Blood. 79. 477-480 (1992)

AKIKO SAKASHITA：“成人 T 细胞白血病中 p53 基因的突变”血液。

HITOSHI SUZUSHIMA et al.: "Discordant gene and surface expression of the T-cell receptor/CD3 complex in adult T-cell leukemia cells." Cancer Res.51. 6084-6088 (1991)

HITOSHI SUZUSHIMA 等人：“成人 T 细胞白血病细胞中 T 细胞受体/CD3 复合物的基因和表面表达不一致。”