Inverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant hemopoiesis

Salomé, M. , Hopcroft, L. and Keeshan, K. (2018) Inverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant hemopoiesis. Experimental Hematology, 66, 63-78.e13. (doi:10.1016/j.exphem.2018.07.005) (PMID:30031847)

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Abstract

TRIBBLES pseudokinases (TRIB1, TRIB2 and TRIB3) are important regulators of normal and malignant haemopoiesis. The relative abundance of each TRIBBLES family member may be important for distinct oncogenic or tumour suppressor functions. We map the expression profiles of TRIB1, TRIB2 and TRIB3 in human and murine haemopoietic stem, progenitor and mature cells and in human leukaemia datasets. Our data show that TRIB1-TRIB2 have an inverse expression relationship in normal haemopoiesis whereas TRIB1-TRIB3 have a positive correlation. We reveal that TRIB3 expression is high in the dormant haemopoietic stem cell (HSC) population, implicating a novel role for TRIB3 in stem cell quiescence. These analyses support a non-redundant role for each TRIBBLES member during normal haemopoietic differentiation. We show that TRIB1-TRIB2 display a significant negative correlation in myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) subtypes, but not in acute lymphoid leukaemia (ALL). This inverse relationship is specific to certain subtypes of AML. A positive correlation exists in different leukaemia subtypes between TRIB1-TRIB3. The TRIB1-TRIB2 and TRIB1-TRIB3 correlations are consistent with a correlative relationship with C/EBP transcription factor family members. Our results have implications for the development of strategies to therapeutically target these genes in different types of leukaemia.

Item Type:Articles
Additional Information:MS was supported by the Friends of Paul O'Gorman. KK was supported by Children with Cancer UK and The Howat Foundation. LEMH was also supported by a Leuka John Goldman Fellowship (Leuka2017/JGF/0003).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Keeshan, Dr Karen and Salome, Ms Mara and Hopcroft, Dr Lisa
Authors: Salomé, M., Hopcroft, L., and Keeshan, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Experimental Hematology
Publisher:Elsevier
ISSN:0301-472X
ISSN (Online):1873-2399
Published Online:20 July 2018
Copyright Holders:Copyright © 2018 ISEH -- Society for Hematology and Stem Cells
First Published:First published in Experimental Hematology 66: 63-78.e13
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
767002Exposing the interdependent mechanisms of the leukaemic stem cell and the leukaemic niche in chronic myeloid leukaemia using integrative network and systems biologyLisa HopcroftThe Kay Kendall Leukaemia Fund (KENDALL)KKL1148RI CANCER SCIENCES