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TitleUsing Cryo-ET to distinguish platelets during pre-acute myeloid leukemia from steady state hematopoiesis.
Journal, issue, pagesCommun Biol, Vol. 5, Issue 1, Page 72, Year 2022
Publish dateJan 20, 2022
AuthorsYuewei Wang / Tong Huo / Yu-Jung Tseng / Lan Dang / Zhili Yu / Wenjuan Yu / Zachary Foulks / Rebecca L Murdaugh / Steven J Ludtke / Daisuke Nakada / Zhao Wang /
PubMed AbstractEarly 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 ...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.
External linksCommun Biol / PubMed:35058565 / PubMed Central
MethodsEM (tomography)
Structure data

EMDB-24287:
Cryo-ET platelet of WT mouse
Method: EM (tomography)

EMDB-24288:
Cryo-ET platelet of AML mouse
Method: EM (tomography)

EMDB-24289:
Cryo-ET platelet of pre-AML mouse
Method: EM (tomography)

EMDB-24291:
Cryo-ET platelet of control mouse (1 week)
Method: EM (tomography)

EMDB-24298:
Cryo-ET platelet of control mouse (3 week)
Method: EM (tomography)

Source
  • Mus musculus (house mouse)

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