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Folylpolyglutamate synthetase inactivation in relapsed ALL induces a druggable folate metabolic vulnerability
Drug Resistance Updates ( IF 15.8 ) Pub Date : 2024-08-16 , DOI: 10.1016/j.drup.2024.101141
Hui Li 1 , Yao Chen 2 , Ming Ding 2 , Jingjing Liu 3 , Huiying Sun 2 , Houshun Fang 2 , Samuel W Brady 3 , Yan Xu 2 , Fabian Glaser 4 , Xiaotu Ma 3 , Yabin Tang 5 , Liang Du 6 , Xiaoyu Wu 2 , Shuxuan Wang 2 , Liang Zhu 5 , Benshang Li 2 , Shuhong Shen 1 , Jinghui Zhang 3 , Liang Zheng 1 , Jiyang Yu 3 , Yehuda G Assaraf 7 , Bin-Bing S Zhou 8
Affiliation  

The antifolate methotrexate (MTX) is an anchor drug used in acute lymphoblastic leukemia (ALL) with poorly understood chemoresistance mechanisms in relapse. Herein we find decreased folate polyglutamylation network activities and inactivating FPGS mutations, both of which could induce MTX resistance and folate metabolic vulnerability in relapsed ALL.

中文翻译:


复发性 ALL 中的叶酰聚谷氨酸合成酶失活诱导可成药的叶酸代谢脆弱性



抗叶酸甲氨蝶呤 (MTX) 是一种用于急性淋巴细胞白血病 (ALL) 的锚定药物,其复发时的化疗耐药机制知之甚少。在此,我们发现叶酸聚谷氨酰化网络活性降低和 FPGS 突变失活,这两者都可能诱导复发性 ALL 中的 MTX 耐药和叶酸代谢脆弱性。
更新日期:2024-08-16
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