The Role of PHF6 in Hematopoiesis and Hematologic Malignancies

Yusra A. Eisa, Ying Guo, Feng Chun Yang

Research output: Contribution to journalReview articlepeer-review

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). [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)67-75
Number of pages9
JournalStem Cell Reviews and Reports
Volume19
Issue number1
DOIs
StatePublished - Jan 2023

Keywords

  • AML
  • BFLS
  • MDS/MPN
  • PHF6
  • Solid tumors
  • T-ALL

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research

Fingerprint

Dive into the research topics of 'The Role of PHF6 in Hematopoiesis and Hematologic Malignancies'. Together they form a unique fingerprint.

Cite this