journal article·2025-12Open access

AP2M1 Amplification Orchestrates Notch‐Mediated Chemoresistance in Hematopoietic Stem Cells of Acute Myeloid Leukemia Patients

Hansong Lee, Eun Kyoung Kim, Hee Young Ju, Chae Rin Lee, Soyul Ahn, Eun‐Sun Kim, Kyungjae Myung, Won Kyu Kim, Su‐Yeon Cho, Yujin Kwon, Dokyoung Kim, Yeuni Yu, Eun Jung Kwon, Hyomin Kim, Seong Ik Mun, Dong Min Lim, Kihun Kim, Hye Jin Heo, Seung Eun Baek, Sun Young Lee, Hyunsoo Cho, Eun Young Choi, Tae Sik Goh, Ninib Baryawno, Dongjun Lee, Ki Sun Jung, Keon Hee Yoo, Chang‐Kyu Oh, Yun Hak Kim

Advanced Science· Volume 12· Issue 48

Abstract

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.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Acute Myeloid Leukemia Research · Epigenetics and DNA Methylation · Hematopoietic Stem Cell Transplantation

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Medical Research Institute Pusan National University Yangsan 50612 Republic of Korea

Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute School of Medicine, Core Research Institute (CRI) Kyung Hee University Seoul 02447 Republic of Korea

Department of Pediatrics Samsung Medical Center Sungkyunkwan University School of Medicine Seoul 06351 Republic of Korea

Department of Convergence Medical Sciences School of Medicine Pusan National University Yangsan 50612 Republic of Korea

Center for Genomic Integrity Institute for Basic Science (IBS) Ulsan 44919 Republic of Korea

Center for Natural Product Efficacy Optimization Korea Institute of Science and Technology (KIST) Gangneung 25451 Republic of Korea

Department of Convergence Medicine Yonsei University Wonju College of Medicine Wonju 26426 Republic of Korea

Division of Natural Product Applied Science University of Science and Technology (UST) Daejeon 34113 Republic of Korea

Department of Precision Medicine Graduate School Kyung Hee University Seoul 02447 Republic of Korea

Interdisciplinary Program of Genomic Data Science Pusan National University Yangsan 50612 Republic of Korea

Department of Anatomy School of Medicine Pusan National University Yangsan 50612 Republic of Korea

Department of Biomedical Informatics School of Medicine Pusan National University Yangsan 50612 Republic of Korea

Department of Internal Medicine Seoul National University Hospital Seoul 03080 Republic of Korea

Department of Biochemistry School of Medicine Pusan National University Yangsan 50612 Republic of Korea

Department of Orthopaedic Surgery Pusan National University Hospital and School of Medicine Pusan National University Busan 49241 Republic of Korea

Childhood Cancer Research Unit Department of Women's and Children's Health Karolinska Institute Stockholm 17177 Sweden

Transplantation Research Center Research Institute for Convergence of Biomedical Science and Technology Pusan National University Yangsan Hospital Yangsan 50612 Republic of Korea

Department of Internal Medicine Pusan National University Yangsan Hospital Pusan National University School of Medicine Yangsan 50612 Republic of Korea

Institute for Future Earth Pusan National University Busan 46241 Republic of Korea

Research Institute for Convergence of Biomedical Science and Technology Pusan National University Yangsan Hospital Yangsan 50612 Republic of Korea

Funding

Daewoong Foundation · National Research Foundation of Korea · Korea Research Environment Open Network

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