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

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 hum...

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Main Authors: Salomé, M, Hopcroft, L, Keeshan, K
Format: Journal article
Language:English
Published: Elsevier 2018
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author Salomé, M
Hopcroft, L
Keeshan, K
author_facet Salomé, M
Hopcroft, L
Keeshan, K
author_sort Salomé, M
collection OXFORD
description 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.
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spelling oxford-uuid:94c40899-ee45-4c29-81a2-2280b76c11362022-03-26T23:41:44ZInverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant hemopoiesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:94c40899-ee45-4c29-81a2-2280b76c1136EnglishSymplectic ElementsElsevier2018Salomé, MHopcroft, LKeeshan, KTRIBBLES 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.
spellingShingle Salomé, M
Hopcroft, L
Keeshan, K
Inverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant hemopoiesis
title Inverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant hemopoiesis
title_full Inverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant hemopoiesis
title_fullStr Inverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant hemopoiesis
title_full_unstemmed Inverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant hemopoiesis
title_short Inverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant hemopoiesis
title_sort inverse and correlative relationships between tribbles genes indicate non redundant functions during normal and malignant hemopoiesis
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AT hopcroftl inverseandcorrelativerelationshipsbetweentribblesgenesindicatenonredundantfunctionsduringnormalandmalignanthemopoiesis
AT keeshank inverseandcorrelativerelationshipsbetweentribblesgenesindicatenonredundantfunctionsduringnormalandmalignanthemopoiesis