Development of new tharapy and search for new cell death mechanism in hematologic malignancies

血液恶性肿瘤新疗法的开发和新细胞死亡机制的探索

• 批准号: 23390273
• 负责人: ADACHI Souichi
• 金额: $ 12.4万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390273/
• 关键词: 難治性血液腫瘍; アポトーシス; オートファジー; 新規予後因子; 白血病幹細胞; 細胞死; 遺伝子変異; 遺伝子発現; 微小残存病変

We have done the following three projects to develop new therapies for chemo-resisitant hematologic malignancies. (1) To search new cell death mechanism of refractory leukemia in vivo (2) To search new prognostic factors in refractory leukemia (3) Analyze function of cells in minimal residual disease (MRD) of AML. (1) We detected autophagic cells in bone marrow, liver, spleen and craniospinal system of NOG mouse transplanted Ph1 ALL leukemic cells after treatment of dasatinib. (2) We analysed KIT mutations in AML-05 samples. Event free survivals are poor and relapse rates are high in KIT mutation positive patients. (3) We detected CD56 expression in CD34+CD33+ precursor cells only in Down syndrome patients and not in non-Down syndrome patients. We have to be carefully analyse MRD detection especially in Down syndrome patients.

我们已经做了以下三个项目，以开发新的治疗化疗无效的血液系统恶性肿瘤。(1)在体内寻找难治性白血病新的细胞死亡机制（2）寻找难治性白血病新的预后因素（3）分析AML微小残留病（MRD）中细胞的功能。(1)我们检测了NOG小鼠移植的Ph 1 ALL白血病细胞经达沙替尼治疗后的骨髓、肝脏、脾脏和颅脊髓系统中的自噬细胞。(2)我们分析了AML-05样品中的KIT突变。KIT突变阳性患者的无事件生存率较差，复发率较高。(3)我们仅在唐氏综合征患者中检测到CD 34 + CD 33+前体细胞中的CD 56表达，而在非唐氏综合征患者中未检测到。我们必须仔细分析MRD检测，特别是唐氏综合征患者。

项目成果

Appropriate dose reduction in induction therapy is essential for the treatment of infants with acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group.

• DOI: 10.1007/s12185-013-1429-2
• 发表时间: 2013-11
• 期刊: International journal of hematology
• 影响因子: 2.1
• 作者: Tomizawa D;Tawa A;Watanabe T;Saito AM;Kudo K;Taga T;Iwamoto S;Shimada A;Terui K;Moritake H;Kinoshita A;Takahashi H;Nakayama H;Kiyokawa N;Isoyama K;Mizutani S;Hara J;Horibe K;Nakahata T;Adachi S
• 通讯作者: Adachi S

京都大学医学研究科人間健康科学系専攻検査応用開発学血液・生体防御研究室

京都大学研究生院医学研究科、人类健康科学系、应用测试和开发实验室、血液和生物防御实验室

GATA2 Mutations in Pediatric Acute Myeloid Leukemia: A Study of the Japanese Childhood AML Cooperative Study Group

小儿急性髓系白血病中的 GATA2 突变：日本儿童 AML 合作研究组的研究

• 发表时间: 2012
• 作者: Shiba N;Adachi S;et al.
• 通讯作者: et al.

High WT1 mRNA expression after induction chemotherapy and FLT3-ITD have prognostic impact in pediatric acute myeloid leukemia: a study of the Japanese Childhood AML Cooperative Study Group

• DOI: 10.1007/s12185-012-1163-1
• 发表时间: 2012-10-01
• 期刊: INTERNATIONAL JOURNAL OF HEMATOLOGY
• 影响因子: 2.1
• 作者: Shimada, Akira;Taki, Tomohiko;Hayashi, Yasuhide
• 通讯作者: Hayashi, Yasuhide

Appropriate dose modification in induction therapy is essential for the treatment of infants with acute myeloid leukemia; A report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG)

诱导治疗中适当的剂量调整对于治疗婴儿急性髓系白血病至关重要；

• 发表时间: 2012
• 作者: Ueta;Y.;Tomizawa D.
• 通讯作者: Tomizawa D.