Context-specific tumor suppression by PHF6

Abstract

In this issue of Blood, McRae et al report that loss of plant homeodomain finger 6 (Phf6) increases the ability of hematopoietic stem and progenitor cells (HSPCs) to sustain long-term engraftment and can specifically synergize with the oncogenic homeobox transcription factor TLX3 to cause lymphoid neoplasms.

Conditional knockout of Phf6 causes increased cycling of HSPCs as well as increased phenotypically defined progenitors and decreased phenotypic hematopoietic stem cells (HSCs). These effects are partially mediated by increased production of interferon (IFN)-α by Phf6 knockout pDCs. Functionally, these alterations are associated with increased long-term competitive repopulation and increased hematologic neoplasms, the latter being dependent upon the cooperating mutation. GFP, green fluorescent protein; PB, peripheral blood; WBC, white blood cell. This figure has been adapted from Figures 4B and 7A in the article by McRae et al that begins on page 1729. Professional illustration by Patrick Lane, ScEYEnce Studios.