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bioRxiv · 10.1101/2021.10.18.464863

Cryo-ET distinguishes platelets during pre-acute myeloid leukemia from steady state hematopoiesis

Wang, Y.·Huo, T.·Tseng, Y.-J.·Dang, L.·Yu, Z.·Yu, W.·Foulks, Z.·Ludtke, S.·Nakada, D.·Wang, Z.
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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.

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Wang, Y., Huo, T., Tseng, Y.-J., Dang, L., Yu, Z., Yu, W., Foulks, Z., Ludtke, S., Nakada, D., Wang, Z.. 2021-10-18. Cryo-ET distinguishes platelets during pre-acute myeloid leukemia from steady state hematopoiesis. https://doi.org/10.1101/2021.10.18.464863

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