Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/119183
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | PHF6 regulates hematopoietic stem and progenitor cells and its loss synergizes with expression of TLX3 to cause leukemia |
Author: | McRae, H.M. Garnham, A.L. Hu, Y. Witkowski, M.T. Corbett, M.A. Dixon, M.P. May, R.E. Sheikh, B.N. Chiang, W. Kueh, A.J. Nguyen, T.A. Man, K. Gloury, R. Aubrey, B.J. Policheni, A. Di Rago, L. Alexander, W.S. Gray, D.H.D. Strasser, A. Hawkins, E.D. et al. |
Citation: | Blood, 2019; 133(16):1729-1741 |
Publisher: | American Society of Hematology |
Issue Date: | 2019 |
ISSN: | 0006-4971 1528-0020 |
Statement of Responsibility: | Helen M. McRae, Alexandra L. Garnham, Yifang Hu, Matthew T. Witkowski, Mark A. Corbett ... Jozef Gécz ... et al. |
Abstract: | Somatically acquired mutations in PHF6 (plant homeodomain finger 6) frequently occur in hematopoietic malignancies and often coincide with ectopic expression of TLX3. However, there is no functional evidence to demonstrate whether these mutations contribute to tumorigenesis. Similarly, the role of PHF6 in hematopoiesis is unknown. We report here that Phf6 deletion in mice resulted in a reduced number of hematopoietic stem cells (HSCs), an increased number of hematopoietic progenitor cells, and an increased proportion of cycling stem and progenitor cells. Loss of PHF6 caused increased and sustained hematopoietic reconstitution in serial transplantation experiments. Interferon-stimulated gene expression was upregulated in the absence of PHF6 in hematopoietic stem and progenitor cells. The numbers of hematopoietic progenitor cells and cycling hematopoietic stem and progenitor cells were restored to normal by combined loss of PHF6 and the interferon α and β receptor subunit 1. Ectopic expression of TLX3 alone caused partially penetrant leukemia. TLX3 expression and loss of PHF6 combined caused fully penetrant early-onset leukemia. Our data suggest that PHF6 is a hematopoietic tumor suppressor and is important for fine-tuning hematopoietic stem and progenitor cell homeostasis. |
Keywords: | Hematopoietic Stem Cells Animals Mice, Knockout Humans Mice Leukemia Homeodomain Proteins Receptors, Interferon Tumor Suppressor Proteins Repressor Proteins Gene Expression Regulation Carcinogenesis |
Rights: | © 2019 by The American Society of Hematology |
DOI: | 10.1182/blood-2018-07-860726 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1029481 http://purl.org/au-research/grants/nhmrc/1084248 http://purl.org/au-research/grants/nhmrc/1003435 http://purl.org/au-research/grants/nhmrc/575512 http://purl.org/au-research/grants/nhmrc/1081421 http://purl.org/au-research/grants/nhmrc/1020363 http://purl.org/au-research/grants/nhmrc/1058344 |
Published version: | http://dx.doi.org/10.1182/blood-2018-07-860726 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.