Molecular mechanisms and therapeutic approach of residual leukemia

残留白血病的分子机制及治疗途径

• 批准号: 19390261
• 负责人: NAOE Tomoki
• 金额: $ 11.98万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19390261/
• 关键词: 白血病; 幹細胞; 化学療法; 耐性; 造血ニッチ; 接着; ホーミング; ニッシェ

To identify the leukemia-propagating stem cell fraction of Philadelphia chro-mosome-positive (Ph+) leukemia, we serially transplanted human leukemia cells from patients with chronic myeloid leukemia blast crisis or Ph+ acute lymphoblastic leukemia into NOD/SCID/IL-2Rcγ^<null> mice. Engrafted cells were almost identical to the original leukemia cells. CD34+CD38-CD19+, CD34+38+CD19+, and CD34-CD38+CD19+ fractions could self-renew and transfer the leukemia, whereas the CD34-CD38+CD19+ fraction did not stably propagate in NOD/SCID mice. These findings suggest that leukemia-repopulating cells in transformed Ph+ leukemia are included in a lineage-committed but multilayered fraction, and that CD34+ leukemia cells potentially emerge from CD34- populations.

为了鉴定费城染色体阳性（Ph+）白血病的白血病增殖干细胞部分，我们将来自慢性髓性白血病急变或Ph+急性淋巴细胞白血病患者的人白血病细胞连续移植到NOD/SCID/IL-2 Rc γ^<null>小鼠中。移植的细胞几乎与原始白血病细胞相同。CD 34 + CD 38 + CD 19+、CD 34 + CD 38+ CD 19+和CD 34-CD 38 + CD 19+组分在NOD/SCID小鼠体内能自我更新并转移白血病细胞，而CD 34-CD 38 + CD 19+组分在NOD/SCID小鼠体内不能稳定增殖。这些研究结果表明，白血病再生细胞转化Ph+白血病包括在一个谱系承诺，但多层的部分，和CD 34+白血病细胞可能出现从CD 34-人口。

项目成果

Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy

• DOI: 10.1007/s12185-008-0221-1
• 发表时间: 2008-12-01
• 期刊: INTERNATIONAL JOURNAL OF HEMATOLOGY
• 影响因子: 2.1
• 作者: Abe, Akihiro;Minami, Yosuke;Naoe, Tomoki
• 通讯作者: Naoe, Tomoki

FLT3/ITD Regulates Leukemia Cell Adhesion throughα4β1 Integrin and Pyk2 Signaling

FLT3/ITD 通过 α4β1 整合素和 Pyk2 信号调节白血病细胞粘附

• 发表时间: 2009
• 作者: Katsumi A;Kiyoi H;Abe A;Naoe T
• 通讯作者: Naoe T

KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation

• DOI: 10.1182/blood-2009-01-199307
• 发表时间: 2009-08-20
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Shiotsu, Yukimasa;Kiyoi, Hitoshi;Naoe, Tomoki
• 通讯作者: Naoe, Tomoki

Ph陽性白血病幹細胞におけるイマチニブ耐性とボルテゾミブによる克服の可能性

Ph 阳性白血病干细胞中的伊马替尼耐药性及其被硼替佐米克服的潜力

• 发表时间: 2009
• 作者: 南陽介、安部明弘;他
• 通讯作者: 他

Treatment with BortezomibOvercomes Resistance to Imatinib in Ph-Leukemia Quiescent Cells

硼替佐米治疗克服了 Ph 白血病静止细胞对伊马替尼的耐药性

• 发表时间: 2009
• 作者: Kuwatsuka Y;Naoe T;et al.
• 通讯作者: et al.