Myelodysplastic neoplasms dissected into indolent, leukaemic and unfavourable subtypes by computational clustering of haematopoietic stem and progenitor cells

Margot F van Spronsen; Sofie Van Gassen; Carolien Duetz; Theresia M Westers; Yvan Saeys; Arjan A van de Loosdrecht

doi:10.1038/s41375-024-02203-z

Myelodysplastic neoplasms dissected into indolent, leukaemic and unfavourable subtypes by computational clustering of haematopoietic stem and progenitor cells

Leukemia. 2024 Mar 8. doi: 10.1038/s41375-024-02203-z. Online ahead of print.

Authors

Margot F van Spronsen¹, Sofie Van Gassen^{2

3}, Carolien Duetz¹, Theresia M Westers¹, Yvan Saeys^{2

3}, Arjan A van de Loosdrecht⁴

Affiliations

¹ Department of Haematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, Amsterdam, Netherlands.
² VIB Inflammation Research Centre, Ghent University, Ghent, Belgium.
³ Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
⁴ Department of Haematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, Amsterdam, Netherlands. a.vandeloosdrecht@amsterdamumc.nl.

PMID: 38459168
DOI: 10.1038/s41375-024-02203-z

Abstract

Myelodysplastic neoplasms (MDS) encompass haematological malignancies, which are characterised by dysplasia, ineffective haematopoiesis and the risk of progression towards acute myeloid leukaemia (AML). Myelodysplastic neoplasms are notorious for their heterogeneity: clinical outcomes range from a near-normal life expectancy to leukaemic transformation or premature death due to cytopenia. The Molecular International Prognostic Scoring System made progress in the dissection of MDS by clinical outcomes. To contribute to the risk stratification of MDS by immunophenotypic profiles, this study performed computational clustering of flow cytometry data of CD34⁺ cells in 67 MDS, 67 AML patients and 49 controls. Our data revealed heterogeneity also within the MDS-derived CD34⁺ compartment. In MDS, maintenance of lymphoid progenitors and megakaryocytic-erythroid progenitors predicted favourable outcomes, whereas expansion of granulocyte-monocyte progenitors increased the risk of leukaemic transformation. The proliferation of haematopoietic stem cells and common myeloid progenitors with downregulated CD44 expression, suggestive of impaired haematopoietic differentiation, characterised a distinct MDS subtype with a poor overall survival. This exploratory study demonstrates the prognostic value of known and previously unexplored CD34⁺ populations and suggests the feasibility of dissecting MDS into a more indolent, a leukaemic and another unfavourable subtype.