Phf6-null hematopoietic stem cells have enhanced self-renewal capacity and oncogenic potentials

Blood Advances
Yueh-Chwen HsuHwei-Fang Tien

Abstract

Plant homeodomain finger gene 6 (PHF6) encodes a 365-amino-acid protein containing 2 plant homology domain fingers. Germline mutations of human PHF6 cause Börjeson-Forssman-Lehmann syndrome, a congenital neurodevelopmental disorder. Loss-of-function mutations of PHF6 are detected in patients with acute leukemia, mainly of T-cell lineage and in a small proportion of myeloid lineage. The functions of PHF6 in physiological hematopoiesis and leukemogenesis remain incompletely defined. To address this question, we generated a conditional Phf6 knockout mouse model and investigated the impact of Phf6 loss on the hematopoietic system. We found that Phf6 knockout mice at 8 weeks of age had reduced numbers of CD4+ and CD8+ T cells in the peripheral blood compared with the wild-type littermates. There were decreased granulocyte-monocytic progenitors but increased Lin-c-Kit+Sca-1+ cells in the marrow of young Phf6 knockout mice. Functional studies, including competitive repopulation unit and serial transplantation assays, revealed an enhanced reconstitution and self-renewal capacity in Phf6 knockout hematopoietic stem cells (HSCs). Aged Phf6 knockout mice had myelodysplasia-like presentations, including decreased platelet counts, megakaryo...Continue Reading

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Citations

May 14, 2020·Current Opinion in Hematology·Satoru Miyagi, Atsushi Iwama
Jul 31, 2020·Cell Cycle·Veronique A J SmitsDaniël O Warmerdam
Dec 1, 2020·Frontiers in Cell and Developmental Biology·Siebe LoontiensTom Taghon
Aug 13, 2021·Frontiers in Oncology·Jason H Kurzer, Olga K Weinberg

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