Genetic and molecular studies on the oncogenesis of hematopoietic malignancies

我们试图澄清造血恶性肿瘤的肿瘤发生，特别是淋巴细胞恶性肿瘤，如成人t细胞白血病（ATL）和多发性骨髓瘤。我们也尝试从染色体异常患者身上建立细胞系。1)我们从高淀粉酶血症患者身上建立了产生淀粉酶的骨髓瘤细胞系（KHM-1）。染色体分析显示近淀粉酶基因位点与abl癌基因位点之间存在易位。该细胞系在IL-6和tnf - α这两种细胞因子的自分泌生长机制下运作。2)在1例急性淋巴细胞白血病患者中建立表达两种癌基因产物c-myc和bcl-2的细胞株（KHM-2B）；14和14；18染色体易位。在这个细胞系中，两个癌基因被两个免疫球蛋白基因的易位激活。3)我们研究了12例急性未分类白血病（AUL）患者免疫球蛋白（Ig）和t细胞受体（TCR）基因的重排和表达。我们的研究结果表明，AUL通常起源于未分化的细胞，这些细胞具有Ig和TCR基因的异常重排和/或表达。4)我们发现p53肿瘤抑制基因在ATL急性期频繁发生突变。这些结果表明p53突变可能与慢性ATL向急性ATL的转变有关。另一方面，急性ATL细胞表面TCR/CD3复合物表达极低，而慢性ATL细胞表面TCR/CD3复合物表达极低。

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.