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

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...

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Bibliographic Details
Published in:Leukemia 2023-08, Vol.37 (8), p.1626-1637
Main Authors: Hou, Shuaibing, Wang, Xiaomin, Guo, Tengxiao, Lan, Yanjie, Yuan, Shengnan, Yang, Shuang, Zhao, Fei, Fang, Aizhong, Liu, Na, Yang, Wanzhu, Chu, Yajing, Jiang, Erlie, Cheng, Tao, Sun, Xiaojian, Yuan, Weiping
Format: Article
Language:English
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Acute lymphoblastic leukemia
Acute myeloid leukemia
Apoptosis
Bcl-2 protein
Blood diseases
Bone marrow
Cancer Research
Cell differentiation
Critical Care Medicine
Epigenetics
Genes
Hematology
Homeobox
Hospitals
Intensive
Internal Medicine
Laboratory animals
Leukemia
Lymphocytes T
Lymphoma
Malignancy
Medical prognosis
Medical research
Medicine
Medicine & Public Health
Mutation
Myeloid cells
NF-κB protein
Nuclear transport
Oncology
Proteins
Runx1 protein
Signal transduction
Stem cells
Therapeutic targets
Translocation
Tumor suppressor genes
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Summary: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.
ISSN:0887-6924
1476-5551
DOI:10.1038/s41375-023-01953-6