{"doi":"10.1101/2021.10.18.464863","title":"Cryo-ET distinguishes platelets during pre-acute myeloid leukemia from steady state hematopoiesis","abstract":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221852,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":331034,"name":"Tong Huo","orcid":"0000-0003-4731-283X","position":1,"is_corresponding":false},{"id":479331,"name":"Yu-Jung Tseng","orcid":"0000-0002-9537-2493","position":2,"is_corresponding":false},{"id":822426,"name":"Lan Dang","orcid":"0000-0002-5704-4552","position":3,"is_corresponding":false},{"id":561593,"name":"Zhili Yu","orcid":"0000-0003-2497-7249","position":4,"is_corresponding":false},{"id":822427,"name":"Wenjuan Yu","orcid":"0000-0002-4834-5740","position":5,"is_corresponding":false},{"id":778992,"name":"Zachary Foulks","orcid":null,"position":6,"is_corresponding":false},{"id":233008,"name":"Steven J. Ludtke","orcid":"0000-0002-1903-1574","position":7,"is_corresponding":false},{"id":230409,"name":"Daisuke Nakada","orcid":"0000-0001-6010-7094","position":8,"is_corresponding":false},{"id":471321,"name":"Zhao Wang","orcid":"0000-0003-4897-9986","position":9,"is_corresponding":false},{"id":822425,"name":"Yuewei Wang","orcid":"0000-0002-6740-8954","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-18T23:53:59.302331Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}