New classification of leukaemic cells by using of biotecnology. (Differential expression of selected genes in human leukaemia leukocytes)

利用生物技术对白血病细胞进行新分类。

• 批准号: 62570289
• 负责人: SHIOSAKA Takahiko
• 金额: $ 1.09万
• 依托单位: Ehime university
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570289/
• 关键词: Leukaemia; Chronic Lymphocytic Leukaemia; cDNA Library; gene expression; HL-60; oncogene; c-myc; TPA; cDNAlibrary; cDNA; library

Tortal cellular RNAs a variety of hematopoietic neoplastic cells and normal lymphocytes werte analyzed for homology with 21 recombinant DNA segments complementary to the specific mRNA of cells from a patient with chronic lymphocytic leukemia. Twenty of the clones(except for clone 8-6G) were not significantly represented in the mRNA from normal lymphocytes. The relative concentration of three clones(6-1E,7-3G and 9-5C) in the RNAs from a variety of normal and leukemic leukocytes and human hematopoietic cell lines were measured by Northern blot hybridization. This showed that 7-3G,6-1E and 9-5C RNA were highly abundant in RNA from hematopoietic neoplastic leukocytes.Expression of these three clones was studied by nucleic acid hybridization in human promyelocytic leukaemia cells (HL-60)treated with chemical inducers of cell differentiation and in primary cells derived from 27 patients with leukaemia or myerodysplastic syndrome. The diffrerentiation of HL-60 cells into macrophage like cells upon induction by 12-o-tetradecanoyl-phorbol-13-acetate(TPA) was accomanied by rapid induction of the expressin of 6-1E nad 7-3G genes.The expression of the 6-1E and /or 7-3G gen was induced by TPA in foyr of 6 samples derived from patients who achieved complete remission, but not in any of the acute nonlymphocytic leukaemia samples from patients who failed to achieve complete remission. These findings suggest that expression of the 6-1E and 7-3G genes is related to macrophage-monocytic differentiation and that alternation of these gene expression in fresh leukaemia cells after one hour of TPA treatment a re of prognostic significance in predicting the responce to therapy.Futhermore, we have shown that different oncogenes(c-myc,c-abl,c-fos and c-Ha -ras) are expressed in different leukaemic types and that alteration of oncogen e expression after addition of TPA varies from one type of leukaemia to another and within a given individual leukaemic type.

我们分析了各种造血肿瘤细胞和正常淋巴细胞的总细胞 RNA 与 21 个重组 DNA 片段的同源性，这些 DNA 片段与慢性淋巴细胞白血病患者细胞的特定 mRNA 互补。 20个克隆（克隆8-6G除外）在正常淋巴细胞的mRNA中没有显着表现。采用Northern印迹杂交法测定了多种正常和白血病白细胞以及人造血细胞系RNA中三个克隆（6-1E、7-3G和9-5C）的相对浓度。这表明7-3G、6-1E和9-5C RNA在来自造血肿瘤性白细胞的RNA中高度丰富。通过核酸杂交，在用细胞分化的化学诱导剂处理的人早幼粒细胞白血病细胞(HL-60)和来自27例白血病或骨髓增生异常综合征患者的原代细胞中研究了这三个克隆的表达。 HL-60 细胞经 12-o-十四烷酰佛波醇-13-乙酸酯 (TPA) 诱导分化为巨噬细胞样细胞，同时快速诱导 6-1E 和 7-3G 基因的表达。在来自获得完全缓解的患者的 6 个样本中，TPA 诱导了 6-1E 和/或 7-3G 基因的表达，但在 来自未能完全缓解的患者的任何急性非淋巴细胞白血病样本。这些发现表明，6-1E 和 7-3G 基因的表达与巨噬细胞-单核细胞分化有关，并且 TPA 治疗一小时后新鲜白血病细胞中这些基因表达的变化对于预测治疗反应具有预后意义。此外，我们还表明，不同的癌基因（c-myc、c-abl、c-fos 和 c-Ha -ras）在不同的细胞中表达。 白血病类型之间存在差异，并且添加 TPA 后癌基因 e 表达的改变在一种白血病类型与另一种白血病类型之间以及在给定的个体白血病类型内有所不同。

项目成果

Shiosaka T.;Sumida H.;Tanaka Y.; Hamada M.; Okuda H.,: "Abnormal gene expression in skeletal muscle of dystrophic chicken."

盐坂 T.；墨田 H.；田中 Y.；

Tanaka Y.;Shiosaka T.;Sakai.I; Kobayashi.Y.: Acta Haematol.Jpn.50. 854-861 (1987)

田中 Y.;盐坂 T.;Sakai.I;

Takahiko Shiosaka and Grady F Saunders: Proc. Natl. Acad. Sci. USA. 79. 4668-4671 (1982)

Takahiko Shiosaka 和 Grady F Saunders：Proc。

Takahiko Shiosaka;Yoshinobu Tanaka and Yuzuru Kobayashi: Br. J. Cancer. 56. 539-544 (1987)

盐坂贵彦；田中义信和小林柚子：Br.

塩坂孝彦、田中理延: 腫瘍と感染.

Takahiko Shiozaka、Rinobu Tanaka：肿瘤和感染。