Emerging treatments for myelodysplastic syndromes: Biological rationales and clinical translation

Rodríguez‐Sevilla, Juan José; Ademà, Vera; Colla, Simona

doi:10.1016/j.xcrm.2023.100940

Cell Reports Medicine

2023

DOI: 10.1016/j.xcrm.2023.100940

|View full text |Cite

Emerging treatments for myelodysplastic syndromes: Biological rationales and clinical translation

Juan José Rodríguez‐Sevilla¹,

Vera Ademà²,

Simona Colla³

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article5

Relationship

Self Cite0

Independent5

Authors

Journals

Cited by 6 publications

References 127 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Hematopoietic stem cells with granulo-monocytic differentiation state overcome venetoclax sensitivity in patients with myelodysplastic syndromes

Rodriguez-Sevilla,

Ganan-Gomez,

et al. 2024

Nat Commun

View full text Add to dashboard Cite

The molecular mechanisms of venetoclax-based therapy failure in patients with acute myeloid leukemia were recently clarified, but the mechanisms by which patients with myelodysplastic syndromes (MDS) acquire secondary resistance to venetoclax after an initial response remain to be elucidated. Here, we show an expansion of MDS hematopoietic stem cells (HSCs) with a granulo-monocytic-biased transcriptional differentiation state in MDS patients who initially responded to venetoclax but eventually relapsed. While MDS HSCs in an undifferentiated cellular state are sensitive to venetoclax treatment, differentiation towards a granulo-monocytic-biased transcriptional state, through the acquisition or expansion of clones with STAG2 or RUNX1 mutations, affects HSCs’ survival dependence from BCL2-mediated anti-apoptotic pathways to TNFα-induced pro-survival NF-κB signaling and drives resistance to venetoclax-mediated cytotoxicity. Our findings reveal how hematopoietic stem and progenitor cell (HSPC) can eventually overcome therapy-induced depletion and underscore the importance of using close molecular monitoring to prevent HSPC hierarchical change in MDS patients enrolled in clinical trials of venetoclax.

show abstract

Hematopoietic stem cells with granulo-monocytic differentiation state overcome venetoclax sensitivity in patients with myelodysplastic syndromes

Rodriguez-Sevilla,

Ganan-Gomez,

et al. 2024

Nat Commun

View full text Add to dashboard Cite

show abstract

Advances in the management of higher-risk myelodysplastic syndromes: future prospects

Gener-Ricos,

Rodriguez-Sevilla,

Urrutia

et al. 2024

Leukemia & Lymphoma

View full text Add to dashboard Cite

Clonal Hematopoiesis, Inflammation, and Hematologic Malignancy

Kanagal-Shamanna,

Beck,

Calvo

2024

Annu. Rev. Pathol. Mech. Dis.

View full text Add to dashboard Cite

Somatic or acquired mutations are postzygotic genetic variations that can occur within any tissue. These mutations accumulate during aging and have classically been linked to malignant processes. Tremendous advancements over the past years have led to a deeper understanding of the role of somatic mutations in benign and malignant age-related diseases. Here, we review the somatic mutations that accumulate in the blood and their connection to disease states, with a particular focus on inflammatory diseases and myelodysplastic syndrome. We include a definition of clonal hematopoiesis (CH) and an overview of the origins and implications of these mutations. In addition, we emphasize somatic disorders with overlapping inflammation and hematologic disease beyond CH, including paroxysmal nocturnal hemoglobinuria and aplastic anemia, focusing on VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Finally, we provide a practical view of the implications of somatic mutations in clinical hematology, pathology, and beyond. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 19 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Emerging treatments for myelodysplastic syndromes: Biological rationales and clinical translation

Cited by 6 publications

References 127 publications

Hematopoietic stem cells with granulo-monocytic differentiation state overcome venetoclax sensitivity in patients with myelodysplastic syndromes

Hematopoietic stem cells with granulo-monocytic differentiation state overcome venetoclax sensitivity in patients with myelodysplastic syndromes

Advances in the management of higher-risk myelodysplastic syndromes: future prospects

Clonal Hematopoiesis, Inflammation, and Hematologic Malignancy

Contact Info

Product

Resources

About