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发表于 2024-6-13 14:01:35
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来自： 中国
橙色雨丝 发表于 2022-10-29 09:00
Sperling AS, Guerra VA, Kennedy JA, Yan Y, Hsu JI, Wang F, Nguyen AT, Miller PG, McConkey ME, Quevedo Barrios VA, Furudate K, Zhang L, Kanagal-Shamanna R, Zhang J, Little L, Gumbs C, Daver N, DiNardo CD, Kadia T, Ravandi F, Kantarjian H, Garcia-Manero G, Futreal PA, Ebert BL, Takahashi K. Lenalidomide promotes the development of TP53-mutated therapy-related myeloid neoplasms. Blood. 2022 Oct 20;140(16):1753-1763. doi: 10.1182/blood.2021014956. PMID: 35512188.
来那度胺促进TP53突变治疗相关髓系肿瘤的发展
Key Points
Exposure to thalidomide analogs, particularly lenalidomide, is associated with increased risk of TP53-mutated myeloid neoplasms.Treatment with lenalidomide but not pomalidomide leads to expansion of preleukemic Trp53-mutant HSPCs due to selective degradation of Ck1α.
There is a growing body of evidence that therapy-related myeloid neoplasms (t-MNs) with driver gene mutations arise in the background of clonal hematopoiesis (CH) under the positive selective pressure of chemo- and radiation therapies. Uncovering the exposure relationships that provide selective advantage to specific CH mutations is critical to understanding the pathogenesis and etiology of t-MNs. In a systematic analysis of 416 patients with t-MN and detailed prior exposure history, we found that TP53 mutations were significantly associated with prior treatment with thalidomide analogs, specifically lenalidomide. We demonstrated experimentally that lenalidomide treatment provides a selective advantage to Trp53-mutant hematopoietic stem and progenitor cells (HSPCs) in vitro and in vivo, the effect of which was specific to Trp53-mutant HSPCs and was not observed in HSPCs with other CH mutations. Because of the differences in CK1α degradation, pomalidomide treatment did not provide an equivalent level of selective advantage to Trp53-mutant HSPCs, providing a biological rationale for its use in patients at high risk for t-MN. These findings highlight the role of lenalidomide treatment in promoting TP53-mutated t-MNs and offer a potential alternative strategy to mitigate the risk of t-MN development.
要点：
*暴露于沙利度胺类似物，尤其是来那度胺，与TP53突变髓系肿瘤的风险增加有关
*来那度胺而非泊马度胺的治疗由于选择性降解Ck1α而导致白血病前期Trp53突变体HSPC的扩增。
越来越多的证据表明，在化疗和放疗的阳性选择压力下，在克隆性造血（CH）的背景下会出现具有驱动性基因突变的治疗相关髓系肿瘤（t-MN）。揭示为特定CH突变提供选择性优势的暴露关系对于理解t-MNs的发病机制和病因至关重要。在对416例t-MN患者的系统分析和详细的既往暴露史中，我们发现TP53突变与沙利度胺类似物（特别是来那度胺）的既往治疗显著相关。我们通过实验证明，来那度胺治疗在体外和体内对Trp53突变的造血干细胞和祖细胞（HSPC）具有选择性优势，其效果对Trp5突变的HSPC具有特异性，而在具有其它CH突变的HSPCs中未观察到。由于CK1α降解的差异，泊马度胺治疗不会提供与Trp53突变型HSPC同等水平的选择性优势，这为其在t-MN高危患者中的应用提供了生物学基础。这些发现突出了来那度胺治疗在促进TP53突变的t-MN中的作用，并为降低t-MN发展的风险提供了潜在的替代策略。
您这段话的意思是泊马度胺就不太会存在来那度胺这样有利于tp53突变细胞生长的缺点吗？ |
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楼主: 橙色雨丝
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，这种情况，cart是目前唯一选择吗？哪家医院治tp53.淋巴瘤复发相对技术成熟?切片活检确诊复发，选择做cart的医院对吗?
有您指导，踏实了
