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Absence of ABL1 exon 2-encoded SH3 residues in BCR::ABL1 destabilizes the autoinhibited kinase conformation and confers resistance to asciminib.

作者信息

Leyte-Vidal Ariel, DeFilippis RosaAnna, Outhwaite Ian R, Kwan Isabelle, Lee Ji Young, Leavitt Carlyn, Miller Kaeli B, Rea Delphine, Rangwala Aziz M, Lou Kevin, Patel Suhana, Alvarez Ailin, Shokat Kevan M, Bahar Ivet, Seeliger Markus A, Shah Neil P

机构信息

Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, 94143, USA.

Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, 33101, USA.

出版信息

Leukemia. 2024 Sep;38(9):2046-2050. doi: 10.1038/s41375-024-02353-0. Epub 2024 Jul 31.

DOI:10.1038/s41375-024-02353-0
PMID:39085402
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11347358/
Abstract
摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/774a/11347358/38c2ccecbadd/41375_2024_2353_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/774a/11347358/f46f32e63354/41375_2024_2353_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/774a/11347358/38c2ccecbadd/41375_2024_2353_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/774a/11347358/f46f32e63354/41375_2024_2353_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/774a/11347358/38c2ccecbadd/41375_2024_2353_Fig2_HTML.jpg

相似文献

1
Absence of ABL1 exon 2-encoded SH3 residues in BCR::ABL1 destabilizes the autoinhibited kinase conformation and confers resistance to asciminib.BCR::ABL1中缺乏ABL1外显子2编码的SH3结构域会破坏自身抑制激酶构象，并赋予对阿斯科利尼布的抗性。
Leukemia. 2024 Sep;38(9):2046-2050. doi: 10.1038/s41375-024-02353-0. Epub 2024 Jul 31.
2
The e13a3 (b2a3) and e14a3 (b3a3) BCR::ABL1 isoforms are resistant to asciminib.e13a3（b2a3）和e14a3（b3a3）BCR::ABL1亚型对阿斯科利尼布耐药。
Leukemia. 2024 Sep;38(9):2041-2045. doi: 10.1038/s41375-024-02314-7. Epub 2024 Jun 15.
3
BCR::ABL1 kinase N-lobe mutants confer moderate to high degrees of resistance to asciminib.BCR::ABL1 激酶 N 端结构域突变体赋予 ASCIMIB 中等到高度的耐药性。
Blood. 2024 Aug 8;144(6):639-645. doi: 10.1182/blood.2023022538.
4
Asciminib antagonizes transplantable BCR::ABL1-positive lymphoid blast crisis in vivo by targeting malignant stem cells.ASCiminib 通过靶向恶性干细胞在体内拮抗可移植的 BCR::ABL1 阳性淋巴母细胞危象。
Leukemia. 2024 Aug;38(8):1825-1830. doi: 10.1038/s41375-024-02320-9. Epub 2024 Jun 21.
5
Mechanisms of resistance to the BCR-ABL1 allosteric inhibitor asciminib.对BCR-ABL1变构抑制剂阿西替尼耐药的机制。
Leukemia. 2017 Dec;31(12):2844-2847. doi: 10.1038/leu.2017.264. Epub 2017 Aug 18.
6
Asciminib is a novel inhibitor of ABL1 and ABL2 gene fusions in ALL but requires the ABL SH3 domain for efficacy.阿西替尼是一种针对急性淋巴细胞白血病中ABL1和ABL2基因融合的新型抑制剂，但发挥疗效需要ABL SH3结构域。
Blood. 2024 Aug 29;144(9):1022-1026. doi: 10.1182/blood.2024024776.
7
Asciminib resistance of a new BCR::ABL1 p.I293_K294insSSLRD mutant detected in a Ph + ALL patient.在一名Ph+急性淋巴细胞白血病患者中检测到的一种新的BCR::ABL1 p.I293_K294insSSLRD突变对阿塞西尼布耐药。
Ann Hematol. 2025 Feb;104(2):1117-1126. doi: 10.1007/s00277-024-06142-8. Epub 2025 Jan 7.
8
The specificity of asciminib, a potential treatment for chronic myeloid leukemia, as a myristate-pocket binding ABL inhibitor and analysis of its interactions with mutant forms of BCR-ABL1 kinase.ASCIMINIB 的特异性，一种治疗慢性髓性白血病的潜在药物，作为一种豆蔻酰口袋结合的 ABL 抑制剂，并分析其与 BCR-ABL1 激酶突变形式的相互作用。
Leuk Res. 2020 Nov;98:106458. doi: 10.1016/j.leukres.2020.106458. Epub 2020 Sep 29.
9
Asciminib as a new option in the treatment of chronic myeloid leukemia.阿塞西尼布作为慢性粒细胞白血病治疗的新选择。
Future Oncol. 2021 Dec;17(36):5003-5005. doi: 10.2217/fon-2021-1174. Epub 2021 Nov 18.
10
Treatment-Emergent Resistance to Asciminib in Chronic Myeloid Leukemia Patients Due to Myristoyl-Binding Pocket-Mutant of Can Be Effectively Overcome with Dasatinib Treatment.慢性髓性白血病患者中因肉豆蔻酰结合口袋突变导致对阿塞西尼布产生治疗中出现的耐药性，可通过达沙替尼治疗有效克服。
Curr Oncol. 2025 Feb 9;32(2):97. doi: 10.3390/curroncol32020097.

引用本文的文献

1
Activity of STAMP inhibitors in rearranged acute lymphoblastic leukemia is dependent on the Abl2 SH3 domain.STAMP抑制剂在重排急性淋巴细胞白血病中的活性依赖于Abl2 SH3结构域。
Blood Neoplasia. 2025 Apr 25;2(3):100109. doi: 10.1016/j.bneo.2025.100109. eCollection 2025 Aug.
2
2025 European LeukemiaNet recommendations for the management of chronic myeloid leukemia.2025年欧洲白血病网慢性髓性白血病管理建议
Leukemia. 2025 Jul 11. doi: 10.1038/s41375-025-02664-w.

本文引用的文献

1
The e13a3 (b2a3) and e14a3 (b3a3) BCR::ABL1 isoforms are resistant to asciminib.e13a3（b2a3）和e14a3（b3a3）BCR::ABL1亚型对阿斯科利尼布耐药。
Leukemia. 2024 Sep;38(9):2041-2045. doi: 10.1038/s41375-024-02314-7. Epub 2024 Jun 15.
2
Asciminib is a novel inhibitor of ABL1 and ABL2 gene fusions in ALL but requires the ABL SH3 domain for efficacy.阿西替尼是一种针对急性淋巴细胞白血病中ABL1和ABL2基因融合的新型抑制剂，但发挥疗效需要ABL SH3结构域。
Blood. 2024 Aug 29;144(9):1022-1026. doi: 10.1182/blood.2024024776.
3
Asciminib in Newly Diagnosed Chronic Myeloid Leukemia.
阿西替尼治疗新诊断的慢性髓性白血病。
N Engl J Med. 2024 Sep 12;391(10):885-898. doi: 10.1056/NEJMoa2400858. Epub 2024 May 31.
4
BCR::ABL1 kinase N-lobe mutants confer moderate to high degrees of resistance to asciminib.BCR::ABL1 激酶 N 端结构域突变体赋予 ASCIMIB 中等到高度的耐药性。
Blood. 2024 Aug 8;144(6):639-645. doi: 10.1182/blood.2023022538.
5
A biophysical framework for double-drugging kinases.双激酶双重靶向的生物物理框架。
Proc Natl Acad Sci U S A. 2023 Aug 22;120(34):e2304611120. doi: 10.1073/pnas.2304611120. Epub 2023 Aug 17.
6
Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL.阿西替尼对比博舒替尼治疗至少两种酪氨酸激酶抑制剂治疗后的慢性期慢性髓性白血病：ASCEMBL 的长期随访。
Leukemia. 2023 Mar;37(3):617-626. doi: 10.1038/s41375-023-01829-9. Epub 2023 Jan 30.
7
Long-Term Molecular Remission after Treatment with Imatinib in a Chronic Myeloid Leukemia Patient with Extreme Thrombocytosis Harboring Rare e14a3 (b3a3) BCR::ABL1 Transcript: A Case Report.慢性髓性白血病伴极重度血小板增多症患者采用伊马替尼治疗后达到长期分子缓解：罕见 e14a3(b3a3)BCR::ABL1 转录本病例报告。
Curr Oncol. 2022 Oct 28;29(11):8171-8179. doi: 10.3390/curroncol29110645.
8
Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants.联合变构抑制剂 ASCiminib 和 Ponatinib 可抑制高度耐药 BCR-ABL1 突变体的出现并恢复疗效。
Cancer Cell. 2019 Oct 14;36(4):431-443.e5. doi: 10.1016/j.ccell.2019.08.004. Epub 2019 Sep 19.
9
The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview.慢性髓性白血病中不同 BCR-ABL1 转录本类型的比例。国际概述。
Leukemia. 2019 May;33(5):1173-1183. doi: 10.1038/s41375-018-0341-4. Epub 2019 Jan 23.
10
The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1.变构抑制剂 ABL001 能够实现对 BCR-ABL1 的双重靶向。
Nature. 2017 Mar 30;543(7647):733-737. doi: 10.1038/nature21702. Epub 2017 Mar 22.