Analysis of the FLT3/FLT3 ligand system in ALL with 11q23 translocations

11q23 易位 ALL 中的 FLT3/FLT3 配体系统分析

• 批准号: 18591187
• 负责人: SUGITA Kanji
• 金额: $ 2.3万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591187/
• 关键词: FLT3; FLT3 ligand; ALL; 11q23 tralslocations

Mechanism of the FLT3 ligand (FL) -induced cell cycle arrest and acquisition of resistance against anti-leukemic drugs in ALL with 11q23 translocations was analyzed. Three days after culture in the presence of FL, KOCL-58 cell line with 11q23 translocation was induced into GO/GI arrest with up-regulation of CDK inhibitor p27 and dephosphorylation of STATS. In FL-induced cell cycle arrest, the cell line showed resistance against daunorubicin (DNR) or cytosine arabinosid (AraC). When cocultured with bone marrow stromal cell line expressing membrane-bound form of FL at high levels, the cell line was induced into GO/GI arrest and showed resistance to DNR or AraC. This effect was partially abrogated in the presence of anti-FL antibody. Thus, ALL cells with 11q23 translocations are induced into quiescent state resistant to chemotherapy in vivo when they adhere to bone marrow stromal cells producing FL irrespective of membrane-bound form or secretary form. This FLT3/FL system may be associated with the formation of minimum residual disease in bone marrow resulting in early relapse of ALL with 11q23 translocations.

分析了FLT 3配体（FL）诱导11 q23易位ALL细胞周期阻滞和获得抗白血病药物耐药的机制。FL可诱导11 q23易位的KOCL-58细胞发生GO/GI阻滞，并上调CDK抑制剂p27的表达和STATs的去磷酸化。在FL诱导的细胞周期阻滞中，该细胞系显示出对柔红霉素（DNR）或阿糖胞苷（AraC）的抗性。当与高水平表达膜结合型FL的骨髓基质细胞系共培养时，该细胞系被诱导进入GO/GI阻滞，并显示对DNR或AraC的抗性。在抗FL抗体的存在下，这种作用被部分消除。因此，当ALL细胞与产生FL的骨髓基质细胞粘附时，无论膜结合形式还是分泌形式，11 q23易位的ALL细胞都被诱导进入对体内化疗抵抗的静止状态。这种FLT 3/FL系统可能与骨髓中最小残留病变的形成有关，导致11 q23易位的ALL的早期复发。

项目成果

Clonotypic analysis of acute lymphoblastic leukemia with a double TEL-AML1 fusion at onset and relapse

TEL-AML1 双融合急性淋巴细胞白血病发病和复发时的克隆型分析

• 发表时间: 2006
• 期刊: Leukemia 20(2)
• 作者: Inukai;Y;Yoko;ta;S;Okamoto;T;et. al.
• 通讯作者: et. al.

Fms-like kinase 3 ligand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents.

Fms 样激酶 3 配体刺激可诱导 MLL 重排的白血病细胞进入对抗白血病药物耐药的静止状态。

• 发表时间: 2007
• 期刊: Cancer Research 67
• 作者: Furuichi Y. Goi K;Inukai T;Sato H;Nemoto A;Takahashi K;Akahane K;Hirose K;Honna H;Kuroda I;Zhang X;Kagami K;Hayashi Y;Harigaya K;Nakazawa S;Sugita K
• 通讯作者: Sugita K

Fms-1ike kinase 3 1igand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents.

Fms-1ike 激酶 3 1igand 刺激可诱导 MLL 重排的白血病细胞进入对抗白血病药物耐药的静止状态。

• 发表时间: 2007
• 期刊: Cancer Res 67
• 作者: Furuichi Y. Goi K;Inukai T;Sato H;Nemoto A;Takahashi K;Akahane K;Hirose K;Honna H;Kuroda I;Zhang X;Kagami K;Hayashi Y;Harigaya K;Nakazawa S;Sugita K
• 通讯作者: Sugita K

Natural pregnancy and delivery after bone marrow transplantation in a Fanconi anemia patient.

范可尼贫血患者骨髓移植后自然妊娠和分娩。

• 发表时间: 2006
• 期刊: Brit H Haematol 135
• 作者: Goi K;Sugita K;Inukai T;et al.
• 通讯作者: et al.

Fms-like kinase 3 ligand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents

Fms 样激酶 3 配体刺激诱导 MLL 重排白血病细胞进入对抗白血病药物耐药的静止状态

• 发表时间: 2007
• 期刊: Cancer Research 67
• 作者: Furuichi;Y.;Goi;K.;Inukai;T.;Sato;H.;Nemoto;A.;Takahashi;K.;Akahane;K.;Hirose;K.;Hanna;H.;Kuroda;I.;Zhang;X.;Kagami;K.;Hayashi;Y.;Harigaya;K.;Nakazawa;S.;Sugita;K
• 通讯作者: K