Prediction of CHOP therapy resistance in diffuse large B cell lymphoma: a genome-wide cDNA microarray analysis.

弥漫性大 B 细胞淋巴瘤 CHOP 治疗耐药性的预测：全基因组 cDNA 微阵列分析。

• 批准号: 15590325
• 负责人: SUZUMIYA Junji
• 金额: $ 2.18万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590325/
• 关键词: non-Hodgkin's lymphoma; Diffuselarge B cell lymphoma; Chemotherapy; CHOP therapy; Chemo-resistance; DNA microarray; 悪性リンパ腫; DLBCL; cDNAマイクロアレイ; mRNA; 非ホジキンシンパ腫; びまん性大細胞型B細胞リンパ腫

[Background and Purpose] The standard therapy is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy for advanced diffuse large B-cell lymphoma (DLBCL) patients. About 80% patients of DLBCL reach the remission by CHOP therapy, but the remain of patients are resistant to this therapy. We studied the difference of genetic characteristics between the chemo-sensitive and chemo-resistant groups using cDNA microarray[Patients and Methods] We selected 6 patients of CHOP-sensitive and 7 of CHOP-resistant DLBCL. We analyzed the gene expression profile of both CHOP-sensitive and CHOP-resistant groups by cDNA microarray using Cancer chip version 4.0 (Takara Bio company, Otsu, Japan).[Results] To clarify CHOP-resistant predictor genes, we chose genes that were differentially expressed between CHOP-resistant and sensitive groups (p<0.05) in student t-test. Moreover, we selected the genes within these genes, which of CHOP-resistant group were differentiated positively or negatively more than three times of that of CHOP-sensitive group. Hierarchical clustering showed the clearly different pattern in CHOP-resistant and sensitive groups using these selected genes. There were 8 up-regulated genes included PRAME (Preferentially expressed antigen of melanoma) in CHOP-resistant group and one down-regulated gene, CD79a in CHOP-sensitive group. Furthermore, we studied the relationship, between the expression of PRAME and clinical course using RT-PCR. PRAME was positive in 23 of 77 patients with DLBCL. The survival of PRAM E positive patients was shorter than that of PRAME negative patients (p=0.0565). PRAME was positive in 12 of 45 patients having disease free survival. The prognosis of PRAME positive patients was significantly poorer than that of negative patients (p=0.037).[Conclusion] The expression of PRAME predicts the resistance of CHOP therapy in DLBCL

[背景与目的]晚期弥漫性大B细胞淋巴瘤（DLBCL）的标准治疗方案是环磷酰胺、阿霉素、长春新碱和泼尼松（CHOP）。约80%的DLBCL患者经CHOP治疗后达到缓解，但仍有部分患者对CHOP治疗耐药。[患者与方法]选择6例CHOP敏感DLBCL患者和7例CHOP耐药DLBCL患者。我们使用Cancer chip version 4.0（Takara Bio company，大津，Japan）通过cDNA微阵列分析了CHOP敏感组和CHOP抗性组的基因表达谱。[结果]筛选出在CHOP耐药组和敏感组中差异表达的基因（p<0.05），以明确CHOP耐药预测基因。此外，我们选择了这些基因中，CHOP耐药组的正或负分化超过CHOP敏感组的3倍的基因。系统聚类显示，在CHOP耐药和敏感组使用这些选定的基因明显不同的模式。CHOP耐药组中有8个基因表达上调，其中包括PRAME（黑色素瘤蛋白表达抗原），CHOP敏感组中有1个基因表达下调，即CD 79 a。同时，我们采用RT-PCR方法研究了PRAME的表达与临床病程的关系。77例DLBCL患者中23例PRAME阳性。PRAME阳性患者的生存期短于PRAME阴性患者（p=0.0565）。PRAME在45例无病生存患者中的12例中呈阳性。PRAME阳性患者的预后明显差于阴性患者（p=0.037）。[结论] PRAME的表达可预测DLBCL对CHOP治疗的耐药性

项目成果

Imbalances of chemokines, chemokine receptors and cytokines in Hodgkin lymphoma: classical Hodgkin lymphoma vs. Hodgkin-like ATLL.

霍奇金淋巴瘤中趋化因子、趋化因子受体和细胞因子的失衡：经典霍奇金淋巴瘤与霍奇金样 ATLL。

• 发表时间: 2003
• 期刊: Int J Cancer 106
• 作者: Ohshima K;Karube K;Hamasaki M;Suefuji H;Tutiya T;Yamaguchi T;Suzumiya J;Kikuchi M
• 通讯作者: Kikuchi M

Phase I study of the combination of irinotecan hydrochloride, carboplatin, and dexamethasone for the treatment of relapsed or refractory malignant lymphoma

• DOI: 10.1532/ijh97.03071
• 发表时间: 2004-04
• 期刊: International Journal of Hematology
• 影响因子: 2.1
• 作者: J. Suzumiya;H. Suzushima;Kouichi Maeda;S. Okamura;A. Utsunomiya;T. Shibuya;K. Tamura;Kyushu Hematology Organization for Treatment Study Group-Kyushu-Hematology-Organization-for-Treatment-Study-147209276

Gene expression in adult T cellleukemia/lymphoma: up-regulation of matrix mettallopreteinase 2 in skin lesions.

成人 T 细胞白血病/淋巴瘤中的基因表达：皮肤病变中基质金属蛋白酶 2 的上调。

• 发表时间: 2004
• 期刊: J Clin Experiment Hematop athol 44
• 作者: Karube K;Ohshima K;Hamasaki M;Tsuchiya T;Yamaguchi T;Suefugi H;Suzumiya J;Nabeshima K;Utsunomiya A;Harada M;Kikuchi M
• 通讯作者: Kikuchi M

Imbalances of chemokines, chemokine receptors and cytokines in Hodgkin lymphoma : classical Hodgkin lymphoma vs.Hodgkin-like ATLL

霍奇金淋巴瘤中趋化因子、趋化因子受体和细胞因子的失衡：经典霍奇金淋巴瘤与霍奇金样 ATLL

• 发表时间: 2003
• 期刊: Int J Cancer 106
• 作者: Ohshima K--;Suzumiya J;(7番目他6名)
• 通讯作者: (7番目他6名)

Clinical and genetic characteristics of Japanese Burkitt lymphomas with or without leukemic presentation

• DOI: 10.1007/bf02986618
• 发表时间: 2003-06-01
• 期刊: INTERNATIONAL JOURNAL OF HEMATOLOGY
• 影响因子: 2.1
• 作者: Namiki, T;Sakashita, A;Kaneko, Y
• 通讯作者: Kaneko, Y