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美国德克萨斯大学西南医学中心Michalis Agathocleous课题组发现，白血病发生对丙酮酸脱氢酶的需求取决于细胞谱系。2021年8月9日，《细胞—代谢》杂志在线发表了这项成果。

研究人员比较了造血和白血病中的葡萄糖代谢情况。与其他造血细胞相比，胸腺T细胞祖细胞偏好葡萄糖，并通过丙酮酸脱氢酶（PDH）在三羧酸循环中氧化了更多的葡萄糖。PDH缺失减少了双阳性T细胞祖细胞，但对造血干细胞、骨髓祖细胞或其他造血细胞没有影响。PDH的缺失阻断了Pten缺陷T细胞白血病的进展，但没有阻断Pten缺陷骨髓类肿瘤的进展。因此，白血病中对PDH的需求反映了正常起源细胞的代谢，与驱动基因病变无关。PDH可用于防止丙酮酸积累，并维持谷胱甘肽水平和氧化还原平衡。

据介绍，癌细胞的代谢与它们相应的正常组织相似。癌症和正常组织之间的差异可能反映了转化过程中的重新编程，或者是维持起源于癌症的特定正常细胞类型的代谢。

附：英文原文

Title: The requirement for pyruvate dehydrogenase in leukemogenesis depends on cell lineage

Author: Sojeong Jun, Swetha Mahesula, Thomas P. Mathews, Misty S. Martin-Sandoval, Zhiyu Zhao, Elena Piskounova, Michalis Agathocleous

Issue&Volume: 2021-08-09

Abstract: Cancer cells are metabolically similar to their corresponding normal tissues. Differencesbetween cancers and normal tissues may reflect reprogramming during transformationor maintenance of the metabolism of the specific normal cell type that originatedthe cancer. Here, we compare glucose metabolism in hematopoiesis and leukemia. ThymusT cell progenitors were glucose avid and oxidized more glucose in the tricarboxylicacid cycle through pyruvate dehydrogenase (PDH) as compared with other hematopoieticcells. PDH deletion decreased double-positive T cell progenitor cells but had no effecton hematopoietic stem cells, myeloid progenitors, or other hematopoietic cells. PDHdeletion blocked the development of Pten-deficient T cell leukemia, but not the development of a Pten-deficient myeloid neoplasm. Therefore, the requirement for PDH in leukemia reflectedthe metabolism of the normal cell of origin independently of the driver genetic lesion.PDH was required to prevent pyruvate accumulation and maintain glutathione levelsand redox homeostasis.

DOI: 10.1016/j.cmet.2021.07.016

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00332-6

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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