2. Academic Validation
  3. PHF6 maintains acute myeloid leukemia via regulating NF-κB signaling pathway

PHF6 maintains acute myeloid leukemia via regulating NF-κB signaling pathway

  • Leukemia. 2023 Jul 1. doi: 10.1038/s41375-023-01953-6.
Shuaibing Hou # 1 2,  Xiaomin Wang # 3 4 5,  Tengxiao Guo # 1 2,  Yanjie Lan 1 6,  Shengnan Yuan 1,  Shuang Yang 1 2,  Fei Zhao 1 2,  Aizhong Fang 6,  Na Liu 7,  Wanzhu Yang 1,  Yajing Chu 1 2,  Erlie Jiang 1 2,  Tao Cheng 1 2,  Xiaojian Sun 7,  Weiping Yuan 8 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
  • 2 Tianjin Institutes of Health Science, Tianjin, 301600, China.
  • 3 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. wangxiaomin@ihcams.ac.cn.
  • 4 Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of lymphoma, Peking University Cancer Hospital & Institute, Beijing, 100039, China. wangxiaomin@ihcams.ac.cn.
  • 5 Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China. wangxiaomin@ihcams.ac.cn.
  • 6 Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
  • 7 State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 8 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. wpyuan@ihcams.ac.cn.
  • 9 Tianjin Institutes of Health Science, Tianjin, 301600, China. wpyuan@ihcams.ac.cn.
  • # Contributed equally.
PMID: 37393343 DOI: 10.1038/s41375-023-01953-6
Abstract

Acute myeloid leukemia (AML) is a major hematopoietic malignancy characterized by the accumulation of immature and abnormally differentiated myeloid cells in bone marrow. Here with in vivo and in vitro models, we demonstrate that the Plant homeodomain finger gene 6 (PHF6) plays an important role in Apoptosis and proliferation in myeloid leukemia. Phf6 deficiency could delay the progression of RUNX1-ETO9a and MLL-AF9-induced AML in mice. PHF6 depletion inhibited the NF-κB signaling pathways by disrupting the PHF6-p50 complex and partially inhibiting the nuclear translocation of p50 to suppress the expression of BCL2. Treating PHF6 over-expressed myeloid leukemia cells with NF-κB Inhibitor (BAY11-7082) significantly increased their Apoptosis and decreased their proliferation. Taken together, in contrast to PHF6 as a tumor suppressor in T-ALL as reported, we found that PHF6 also plays a pro-oncogenic role in myeloid leukemia, and thus potentially to be a therapeutic target for treating myeloid leukemia patients.

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