Cord blood-derived quiescent CD34+ cells are more transcriptionally matched to AML blasts than cytokine-induced normal human hematopoietic CD34+ cells

Munje, Chinmay, Hills, Robert K. ORCID: https://orcid.org/0000-0003-0166-0062, Whetton, Anthony, Burnett, Alan K., Darley, Richard L. ORCID: https://orcid.org/0000-0003-0879-0724 and Tonks, Alex ORCID: https://orcid.org/0000-0002-6073-4976 2015. Cord blood-derived quiescent CD34+ cells are more transcriptionally matched to AML blasts than cytokine-induced normal human hematopoietic CD34+ cells. Gene Expression: International Journal of Molecular and Cellular Science 16 (4) , pp. 169-175. 10.3727/105221615X14399878166159

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Abstract

Acute myeloid leukemia (AML) is characterized by developmental arrest, which is thought to arise from transcriptional dysregulation of myeloid development programs. Hematopoietic stem and progenitor cells (HSPCs) isolated from human blood are frequently used as a normal comparator in AML studies. Previous studies have reported changes in the transcriptional program of genes involved in proliferation, differentiation, apoptosis, and homing when HSPCs were expanded ex vivo. The intrinsic functional differences between quiescent and dividing CD34+ HSPCs prompted us to determine whether fresh or cytokine-induced cord blood-derived CD34+ HSPCs are a more appropriate normal control compared to AML blasts. Based on principal component analysis and gene expression profiling we demonstrate that CD34+ HSPCs that do not undergo ex vivo expansion are transcriptionally similar to minimally differentiated AML blasts. This was confirmed by comparing the cell cycle status of the AML blasts and the HSPCs. We suggest that freshly isolated CD34+ HSPCs that do not undergo ex vivo expansion would serve as a better control to identify novel transcriptional targets in the AML blast population.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Acute myeloid leukemia (AML); Cell cycle; Gene expression profiling; Hematopoietic stem cells
Publisher:	Cognizant Communication Corporation
ISSN:	1052-2166
Funders:	Bloodwise
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	17 August 2015
Last Modified:	05 May 2023 06:58
URI:	https://orca.cardiff.ac.uk/id/eprint/78575

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