| First Author | Jalnapurkar SS | Year | 2024 |
| Journal | Leukemia | Volume | 38 |
| Issue | 9 | Pages | 1938-1948 |
| PubMed ID | 39004675 | Mgi Jnum | J:353567 |
| Mgi Id | MGI:7715344 | Doi | 10.1038/s41375-024-02340-5 |
| Citation | Jalnapurkar SS, et al. (2024) PHF6 suppresses self-renewal of leukemic stem cells in AML. Leukemia 38(9):1938-1948 |
| abstractText | Acute myeloid leukemia is characterized by uncontrolled proliferation of self-renewing myeloid progenitors accompanied by a differentiation arrest. PHF6 is a chromatin-binding protein mutated in myeloid leukemias, and its isolated loss increases mouse HSC self-renewal without malignant transformation. We report here that Phf6 knockout increases the aggressiveness of Hoxa9-driven AML over serial transplantation, and increases the frequency of leukemia initiating cells. We define the in vivo hierarchy of Hoxa9-driven AML and identify a population that we term the "LIC-e" (leukemia initiating cells enriched) population. We find that Phf6 loss expands the LIC-e population and skews its transcriptome to a more stem-like state; concordant transcriptome shifts are also observed on PHF6 knockout in a human AML cell line and in PHF6 mutant patient samples from the BEAT AML dataset. We demonstrate that LIC-e accumulation in Phf6 knockout AML occurs not due to effects on cell cycle or apoptosis, but due to an increase in the fraction of its progeny that retain LIC-e identity. Our work indicates that Phf6 loss increases AML self-renewal through context-specific effects on leukemia stem cells. |
