Lee, Hansong Kim, Eun Kyoung Ju, Hee Young Lee, Chae Rin Ahn, Soyul Kim, Eun-Sun Myung, Kyungjae Kim, Won Kyu Cho, Su-Yeon Kwon, Yujin Kim, Dokyoung Yu, Yeuni Kwon, Eun Jung Kim, Hyomin Mun, Seong Ik Lim, Dong Min Kim, Kihun Heo, Hye Jin Baek, Seung Eun Lee, Sun Young Cho, Hyunsoo Choi, Eun Young Goh, Tae Sik Baryawno, Ninib Lee, Dongjun Jung, Ki Sun Yoo, Keon Hee Oh, Chang-Kyu Kim, Yun Hak 2025-11-21T00:07:26Z 2025-11-21T00:07:26Z 2025-11-11 2025-12 https://pubs.kist.re.kr/handle/201004/153551 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. English Wiley-VCH Verlag AP2M1 Amplification Orchestrates Notch-Mediated Chemoresistance in Hematopoietic Stem Cells of Acute Myeloid Leukemia Patients Article 10.1002/advs.202514566 1 Advanced Science, v.12, no.48 Advanced Science 12 48 Y scie scopus 001591851900001 2-s2.0-105018694032 Chemistry, Multidisciplinary Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article SIGNALING PATHWAY DISEASE AML chemoresistance HSPC NOTCH