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- Title
Using Cryo-ET to distinguish platelets during pre-acute myeloid leukemia from steady state hematopoiesis.
- Authors
Wang, Yuewei; Huo, Tong; Tseng, Yu-Jung; Dang, Lan; Yu, Zhili; Yu, Wenjuan; Foulks, Zachary; Murdaugh, Rebecca L.; Ludtke, Steven J.; Nakada, Daisuke; Wang, Zhao
- Abstract
Early diagnosis of acute myeloid leukemia (AML) in the pre-leukemic stage remains a clinical challenge, as pre-leukemic patients show no symptoms, lacking any known morphological or numerical abnormalities in blood cells. Here, we demonstrate that platelets with structurally abnormal mitochondria emerge at the pre-leukemic phase of AML, preceding detectable changes in blood cell counts or detection of leukemic blasts in blood. We visualized frozen-hydrated platelets from mice at different time points during AML development in situ using electron cryo-tomography (cryo-ET) and identified intracellular organelles through an unbiased semi-automatic process followed by quantitative measurement. A large proportion of platelets exhibited changes in the overall shape and depletion of organelles in AML. Notably, 23% of platelets in pre-leukemic cells exhibit abnormal, round mitochondria with unfolded cristae, accompanied by a significant drop in ATP levels and altered expression of metabolism-related gene signatures. Our study demonstrates that detectable structural changes in pre-leukemic platelets may serve as a biomarker for the early diagnosis of AML. Wang et al characterise platelets in a mouse model of acute myeloid leukemia (AML) using Cryo-electron tomography (Cryo-ET) and find that 23% of platelets in pre-leukemic cells exhibit abnormal, round mitochondria with unfolded cristae. They also detect reduced ATP levels and altered expression of metabolism-related genes, altogether suggesting that platelet alterations may serve as a biomarker for AML.
- Publication
Communications Biology, 2022, Vol 5, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-022-03009-4