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The Role of PHF6 in Hematopoiesis and Hematologic Malignancies

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Abstract

Epigenetic regulation of gene expression represents an important mechanism in the maintenance of stem cell function. Alterations in epigenetic regulation contribute to the pathogenesis of hematological malignancies. Plant homeodomain finger protein 6 (PHF6) is a member of the plant homeodomain (PHD)-like zinc finger family of proteins that is involved in transcriptional regulation through the modification of the chromatin state. Germline mutation of PHF6 is the causative genetic alteration of the X-linked mental retardation Borjeson–Forssman–Lehmann syndrome (BFLS). Somatic mutations in PHF6 are identified in human leukemia, such as adult T-cell acute lymphoblastic leukemia (T-ALL, ~ 38%), pediatric T-ALL (~ 16%), acute myeloid leukemia (AML, ~ 3%), chronic myeloid leukemia (CML, ~ 2.5%), mixed phenotype acute leukemia (MPAL, ~ 20%), and high-grade B-cell lymphoma (HGBCL, ~ 3%). More recent studies imply an oncogenic effect of PHF6 in B-cell acute lymphoblastic leukemia (B-ALL) and solid tumors. These data demonstrate that PHF6 could act as a double-edged sword, either a tumor suppressor or an oncogene, in a lineage-dependent manner. However, the underlying mechanisms of PHF6 in normal hematopoiesis and leukemogenesis remain largely unknown. In this review, we summarize current knowledge of PHF6, emphasizing the role of PHF6 in hematological malignancies.

Graphical abstract

Epigenetic regulation of PHF6 in B-ALL. PHF6 maintains a chromatin structure that is permissive to B-cell identity genes, but not T-cell-specific genes (left). Loss of PHF6 leads to aberrant expression of B-cell- and T-cell-specific genes resulting from lineage promiscuity and binding of T-cell transcription factors (right).

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Funding

This work was supported by grants from the National Institutes of Health (HL149318, HL158081, and CA172408 to F.-C.Y.).

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  1. Department of Cell Systems & Anatomy, University of Texas Health San Antonio, San Antonio, TX, USA

    Yusra A. Eisa, Ying Guo & Feng-Chun Yang

  2. Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA

    Feng-Chun Yang

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Yusra A. Eisa, Ying Guo and Feng-Chun Yang wrote the manuscript and gave final approval of the manuscript.

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Eisa, Y.A., Guo, Y. & Yang, FC. The Role of PHF6 in Hematopoiesis and Hematologic Malignancies. Stem Cell Rev and Rep 19, 67–75 (2023). https://doi.org/10.1007/s12015-022-10447-4

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