Journal Article

DKFZ-2022-00071

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetic barcoding systematically comparing genes in del(5q) MDS reveals a central role for CSNK1A1 in clonal expansion.

Stalmann, U. S. A. ; Ticconi, F. ; Snoeren, I. A. M. ; Li, R. ; Gleitz, H. ; Cowley, G. ; McConkey, M. E. ; Wong, A. B. ; Schmitz, S. ; Fuchs, S. N. R. ; Sood, S.DKFZ* ; Leimkühler, N. B. ; Martinez-Høyer, S. ; Banjanin, B. ; Root, D. E. ; Brümmendorf, T. H. ; Pearce, J. ; Schuppert, A. ; Bindels, E. ; Essers, M.DKFZ* ; Heckl, D. ; Stiehl, T. P. ; Costa, I. G. ; Ebert, B. L. ; Schneider, R. K.

2022
American Society of Hematology Washington, DC

This record in other databases:  

Please use a persistent id in citations: doi:10.1182/bloodadvances.2021006061

Abstract: How genetic haploinsufficiency contributes to the clonal dominance of hematopoietic stem cells (HSC) in del(5q) myelodysplastic syndrome (MDS) remains unresolved. Using a genetic barcoding strategy, a systematic comparison was carried out on genes implicated in the pathogenesis of del(5q) MDS in direct competition with each other and wild-type (WT) cells with single clone resolution. Csnk1a1 haploinsufficient HSCs expanded (oligo)clonally and outcompeted all other tested genes and combinations. Csnk1a1-/+ multipotent progenitors showed a pro-proliferative gene signature and HSCs a downregulation of inflammatory signaling/immune response. In validation experiments, Csnk1a1-/+ HSCs outperformed their WT counterparts under a chronic inflammation stimulus, also known to be caused by neighboring genes on chromosome 5. A crucial role for Csnk1a1 haploinsufficiency in the selective advantage of the 5q- HSC is therefore proposed. It is implemented by creation of a unique competitive advantage through increased HSC self-renewal and proliferation capacity, as well as increased fitness under inflammatory stress.

Note: 2022 Mar 22;6(6):1780-1796

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Contributing Institute(s):

1. A011 Stressinduzierte Aktivierung von hämatopoetischen Stammzellen (A011)
2. V960 HI-Stem (V960)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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