PUBLICATION
AP2M1 Amplification Orchestrates Notch-Mediated Chemoresistance in Hematopoietic Stem Cells of Acute Myeloid Leukemia Patients
- Authors
- Lee, H., Kim, E.K., Ju, H.Y., Lee, C.R., Ahn, S., Kim, E.S., Myung, K., Kim, W.K., Cho, S.Y., Kwon, Y., Kim, D., Yu, Y., Kwon, E.J., Kim, H., Mun, S.I., Lim, D.M., Kim, K., Heo, H.J., Baek, S.E., Lee, S.Y., Cho, H., Choi, E.Y., Goh, T.S., Baryawno, N., Lee, D., Jung, K.S., Yoo, K.H., Oh, C.K., Kim, Y.H.
- ID
- ZDB-PUB-251014-13
- Date
- 2025
- Source
- Advanced science (Weinheim, Baden-Wurttemberg, Germany) : e14566e14566 (Journal)
- Registered Authors
- Keywords
- AML, AP2M1, HSPC, NOTCH, chemoresistance
- Datasets
- GEO:GSE236393
- MeSH Terms
-
- Adaptor Protein Complex 2*/genetics
- Adaptor Protein Complex 2*/metabolism
- Animals
- Cell Line, Tumor
- Drug Resistance, Neoplasm*/genetics
- Female
- Hematopoietic Stem Cells*/metabolism
- Humans
- Leukemia, Myeloid, Acute*/drug therapy
- Leukemia, Myeloid, Acute*/genetics
- Leukemia, Myeloid, Acute*/metabolism
- Leukemia, Myeloid, Acute*/pathology
- Male
- Neoplastic Stem Cells/metabolism
- Receptor, Notch1*/genetics
- Receptor, Notch1*/metabolism
- Signal Transduction
- Zebrafish
- PubMed
- 41082341 Full text @ Adv Sci (Weinh)
Citation
Lee, H., Kim, E.K., Ju, H.Y., Lee, C.R., Ahn, S., Kim, E.S., Myung, K., Kim, W.K., Cho, S.Y., Kwon, Y., Kim, D., Yu, Y., Kwon, E.J., Kim, H., Mun, S.I., Lim, D.M., Kim, K., Heo, H.J., Baek, S.E., Lee, S.Y., Cho, H., Choi, E.Y., Goh, T.S., Baryawno, N., Lee, D., Jung, K.S., Yoo, K.H., Oh, C.K., Kim, Y.H. (2025) AP2M1 Amplification Orchestrates Notch-Mediated Chemoresistance in Hematopoietic Stem Cells of Acute Myeloid Leukemia Patients. Advanced science (Weinheim, Baden-Wurttemberg, Germany). :e14566e14566.
Abstract
Acute myeloid leukemia (AML) is a complex hematological malignancy characterized by chemotherapy resistance, leading to poor patient outcomes. This study investigates the role of adaptor protein complex 2 subunit mu 1 (AP2M1) in hematopoiesis and drug response. Utilizing multimodal analyses on bone marrow samples from AML patients and healthy controls, zebrafish models, and human AML cell lines, it is identified that dysregulation of AP2M1 impairs hematopoietic stem and progenitor cell (HSPC) development, underscoring its critical role in hematopoiesis. AP2M1 expression distinctly differentiates normal from malignant cells, surpassing well-recognized cancer stem cell markers, ATP-binding cassette transporters, known for drug efflux and chemoresistance. Elevated AP2M1 levels in AML HSPCs correlate with poor clinical outcomes, as its overexpression reduces apoptosis, enhances stemness, and increases drug resistance. In vivo experiments reveal that AP2M1 directly modulates Notch1 expression, amplifying pro-tumorigenic effects through the Notch1 signaling pathway. These findings highlight the pivotal role of AP2M1 in AML pathogenesis, primarily through its regulation of NOTCH1 expression and signaling cascades. These findings unravel AP2M1 as a previously unrecognized factor in AML pathogenesis and suggest a treatment strategy for AML, focusing on the AP2M1-NOTCH1 axis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping