Using Cryo-ET to distinguish platelets during pre-acute myeloid leukemia from steady state hematopoiesis.
Yuewei WangTong HuoYu-Jung TsengLan DangZhili YuWenjuan YuZachary FoulksRebecca L MurdaughSteven J LudtkeDaisuke NakadaZhao WangPublished in: Communications biology (2022)
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.
Keyphrases
- acute myeloid leukemia
- allogeneic hematopoietic stem cell transplantation
- high resolution
- induced apoptosis
- end stage renal disease
- electron microscopy
- cell cycle arrest
- machine learning
- cell death
- chronic kidney disease
- reactive oxygen species
- endoplasmic reticulum stress
- endoplasmic reticulum
- deep learning
- prognostic factors
- physical activity
- cell proliferation
- skeletal muscle
- signaling pathway
- peripheral blood
- acute lymphoblastic leukemia
- label free
- mesenchymal stem cells
- wild type
- high fat diet induced
- drug induced