CLL耐药的新机制：第二代和非共价BTK抑制剂的变异BTK突变。

IF 21 1区医学 Q1 HEMATOLOGY

Blood Pub Date : 2025-03-06 DOI:10.1182/blood.2024026672

Constantine S Tam, Shalini Balendran, Piers Blombery

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引用次数: 0

摘要

BTK抑制剂（BTKi）是CLL治疗的既定标准。共价的BTKi ibrutinib、acalabrutinib和zanubrutinib与BTK C481结合，均易受C481S突变的影响。包括匹托鲁替尼在内的非共价BTKi克服了C481S耐药，但与多种变异（非c481） BTK突变相关，包括与阿卡拉布替尼和扎努布鲁替尼耐药相关的突变（T474密码子和L528W突变）。我们回顾了目前关于变异BTK突变的知识，讨论了它们的临床意义，并考虑了它们对临床试验的影响。

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Novel mechanisms of resistance in CLL: variant BTK mutations in second-generation and noncovalent BTK inhibitors.

Abstract: Bruton tyrosine kinase inhibitors (BTKis) are an established standard of care in chronic lymphocytic leukemia. The covalent BTKis ibrutinib, acalabrutinib, and zanubrutinib bind to BTK C481 and are all susceptible to the C481S mutation. Noncovalent BTKi, including pirtobrutinib, overcome C481S resistance but are associated with multiple variant (non-C481) BTK mutations, including those associated with resistance to acalabrutinib and zanubrutinib (T474 codon and L528W mutations). We review the current knowledge on variant BTK mutations, discuss their clinical implications, and consider their impact on clinical trials.

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来源期刊

Blood 医学-血液学

CiteScore

23.60

自引率

3.90%

发文量

955

审稿时长

1 months

期刊介绍： Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.