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. 2022 Mar 16:12:815037.
doi: 10.3389/fonc.2022.815037. eCollection 2022.

The Coming of Age of Preclinical Models of MDS

Wei Liu  1 , Patric Teodorescu  2 , Stephanie Halene  1 , Gabriel Ghiaur  2
Affiliations

The Coming of Age of Preclinical Models of MDS

Wei Liu et al. Front Oncol. .

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone-marrow diseases with ineffective hematopoiesis resulting in cytopenias and morphologic dysplasia of hematopoietic cells. MDS carry a wide spectrum of genetic abnormalities, ranging from chromosomal abnormalities such as deletions/additions, to recurrent mutations affecting the spliceosome, epigenetic modifiers, or transcription factors. As opposed to AML, research in MDS has been hindered by the lack of preclinical models that faithfully replicate the complexity of the disease and capture the heterogeneity. The complex molecular landscape of the disease poses a unique challenge when creating transgenic mouse-models. In addition, primary MDS cells are difficult to manipulate ex vivo limiting in vitro studies and resulting in a paucity of cell lines and patient derived xenograft models. In recent years, progress has been made in the development of both transgenic and xenograft murine models advancing our understanding of individual contributors to MDS pathology as well as the complex primary interplay of genetic and microenvironment aberrations. We here present a comprehensive review of these transgenic and xenograft models for MDS and future directions.

Keywords: humanized mouse models; immunodeficient mouse models; myelodysplastic syndromes (MDS); transgenic mouse models; xenograft animal model.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Genetic mouse models of MDS. Using various approaches, these animals allow modeling of MDS in immune competent hosts and in the presence of the endogenous, often unmutated microenvironment. They also provide the analytical tools to study how various mutations impact stem cell function and clonal dominance. Their major shortcoming is that they don’t capture the genetic heterogeneity of MDS. (B) Xenograft mouse models of MDS. Using patient-derived MDS cells, these animals allow modeling of genetically complex disease and the study of clonal architecture and clonal evolution. Most recent humanized immunodeficient mice can even model erythroid maturation, though limited generation of neutrophils and platelets are thus far a major limitation. Created with BioRender.com.
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