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CHRO-MOSOME阳性（pH+）白血病的白血病促进干细胞分数，我们从患有慢性骨髓性白血病或pH+ pH+急性淋巴细胞淋巴细胞白血病患者的患者中串行移植的人白血病细胞，成为NOD/SCID/SCID/SCID/SCID/IL-IL-2RCCRCγ^<null> Mice。植入的细胞几乎与原始白血病细胞相同。 CD34+CD38-CD19+，CD34+38+CD19+，CD34-CD38+CD19+分数可以自我更新和转移白血病，而CD34-CD38+CD19+分数在NOD/SCID小鼠中并不稳定地传播。这些发现表明，转化后的pH+白血病中的白血病 - 抑制细胞包括在谱系合作但多层的分数中，并且CD34+白血病细胞可能会从CD34种群中出现。

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

LRP16 is fused to RUNX1 in monocytic leukemia cell line with t(11;21)(q13;q22)

• DOI: 10.1111/j.1600-0609.2007.00858.x
• 发表时间: 2007-07-01
• 期刊: EUROPEAN JOURNAL OF HAEMATOLOGY
• 影响因子: 3.1
• 作者: Imagama, Shizuka;Abe, Akihiro;Naoe, Tomoki
• 通讯作者: Naoe, Tomoki