Using Cryo-Et to Distinguish Platelets During Pre-acute Myeloid Leukemia From Steady State Hematopoiesis

Authors

Yuewei Wang
Tong Huo
Yu-Jung Tseng
Lan Dang
Zhili Yu
Wenjuan Yu
Zachary Foulks
Rebecca L Murdaugh
Steven J Ludtke
Daisuke Nakada
Zhao Wang

Publication Date

1-20-2022

Journal

Communications Biology

DOI

10.1038/s42003-022-03009-4

PMID

PMC8776871

PMCID

35058565

PubMedCentral® Posted Date

1-20-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Blood Platelets, Female, Hematopoiesis, Leukemia, Myeloid, Acute, Mice, Tomography, X-Ray Computed, Cryoelectron tomography, Cancer screening

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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