Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1.
1/5 보강
PICO 자동 추출 (휴리스틱, conf 2/4)
유사 논문P · Population 대상 환자/모집단
환자: AML, which revealed mutations in ubiquitin ligase family genes in 11
I · Intervention 중재 / 시술
추출되지 않음
C · Comparison 대조 / 비교
추출되지 않음
O · Outcome 결과 / 결론
We found that FBXO11 interacts with and catalyzes K63-linked ubiquitination of LONP1 in the cytosol, to promote LONP1 entry into mitochondria.
Acute myeloid leukemia (AML) is an aggressive cancer with very poor outcomes.
APA
Kincross H, Mo YA, et al. (2026). Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1.. The Journal of clinical investigation, 136(2). https://doi.org/10.1172/JCI181943
MLA
Kincross H, et al.. "Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1.." The Journal of clinical investigation, vol. 136, no. 2, 2026.
PMID
41289019 ↗
Abstract 한글 요약
Acute myeloid leukemia (AML) is an aggressive cancer with very poor outcomes. To identify additional drivers of leukemogenesis, we analyzed sequencing data from 1,727 unique individual patients with AML, which revealed mutations in ubiquitin ligase family genes in 11.2% of samples from adult patients with AML with mutual exclusivity. The SKP1/CUL1/F-box (SCF) E3 ubiquitin ligase complex gene, FBXO11, was the most significantly downregulated gene of the SCF complex in AML. We found that FBXO11 interacts with and catalyzes K63-linked ubiquitination of LONP1 in the cytosol, to promote LONP1 entry into mitochondria. We show that depletion of FBXO11 or LONP1 reduced mitochondrial respiration through impaired LONP1 chaperone activity to assemble electron transport chain Complex IV. Reduced mitochondrial respiration secondary to FBXO11 or LONP1 depletion imparted myeloid-biased stem cell properties in primary CD34+ hematopoietic stem and progenitor cells (HSPCs) in vitro. In a human xenograft model, depletion of FBXO11 cooperated with AML1-ETO and mutant KRASG12D to generate serially transplantable AML. Our findings suggest that reduced FBXO11 cooperates to initiate AML by priming HSPC for myeloid-biased self renewal through attenuation of LONP1-mediated regulation of mitochondrial respiration.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Humans
- Leukemia
- Myeloid
- Acute
- F-Box Proteins
- Animals
- Mice
- Neoplastic Stem Cells
- Mitochondrial Proteins
- Mitochondria
- Alcohol Oxidoreductases
- Female
- Gene Expression Regulation
- Leukemic
- Protein-Arginine N-Methyltransferases
- Male
- Ubiquitination
- Neoplasm Proteins
- Cell Line
- Tumor
- Hematology
- Hematopoietic stem cells
- Leukemias
- Stem cells
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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