PU.1 is linking the glycolytic enzyme HK3 in neutrophil differentiation and survival of APL cells

Federzoni, Elena A; Valk, Peter J M; Torbett, Bruce E; Haferlach, Torsten; Löwenberg, Bob; Fey, Martin F; Tschan, Mario P (2012). PU.1 is linking the glycolytic enzyme HK3 in neutrophil differentiation and survival of APL cells. Blood, 119(21), pp. 4963-70. Washington, D.C.: American Society of Hematology 10.1182/blood-2011-09-378117

Full text not available from this repository. (Request a copy)

The transcription factor PU.1 is a master regulator of myeloid differentiation and function. On the other hand, only scarce information is available on PU.1-regulated genes involved in cell survival. We now identified the glycolytic enzyme hexokinase 3 (HK3), a gene with cytoprotective functions, as transcriptional target of PU.1. Interestingly, HK3 expression is highly associated with the myeloid lineage and was significantly decreased in acute myeloid leukemia patients compared with normal granulocytes. Moreover, HK3 expression was significantly lower in acute promyelocytic leukemia (APL) compared with non-APL patient samples. In line with the observations in primary APL patient samples, we observed significantly higher HK3 expression during neutrophil differentiation of APL cell lines. Moreover, knocking down PU.1 impaired HK3 induction during neutrophil differentiation. In vivo binding of PU.1 and PML-RARA to the HK3 promoter was found, and PML-RARA attenuated PU.1 activation of the HK3 promoter. Next, inhibiting HK3 in APL cell lines resulted in significantly reduced neutrophil differentiation and viability compared with control cells. Our findings strongly suggest that HK3 is: (1) directly activated by PU.1, (2) repressed by PML-RARA, and (3) functionally involved in neutrophil differentiation and cell viability of APL cells.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Fey, Martin and Tschan, Mario

ISSN:

0006-4971

Publisher:

American Society of Hematology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:23

Last Modified:

06 Dec 2013 13:29

Publisher DOI:

10.1182/blood-2011-09-378117

PubMed ID:

22498738

Web of Science ID:

000299597103291

URI:

https://boris.unibe.ch/id/eprint/8069 (FactScience: 213524)

Actions (login required)

Edit item Edit item
Provide Feedback