Higher-risk myelodysplastic syndromes with del(5q): does the del(5q) matter?

ABSTRACT

Introduction: Myelodysplastic Syndrome (MDS) represents a group of cancers characterized by abnormal blood cell formation and maturation, leading to various degrees of cytopenias and potential transformation to acute myeloid leukemia. Deletion of the long arm of chromosome 5 (del(5q)) is the most common clonal chromosomal anomaly in MDS, yet the population in this disease subtype is quite heterogeneous. This manuscript analyzes literature on high-risk MDS with del(5q) abnormalities.

Areas covered: The paper will review outcomes with lenalidomide among high-risk MDS patients with del(5q). It will discuss the implications of harboring TP53 gene mutations, and share the data for allogeneic hematopoietic stem cell transplantations in this setting. Finally, the report evaluates the risk of disease progression in these patients.

Expert commentary: Improved characterization of MDS has enhanced our understanding of patients with anomalies involving del(5q). Emerging literature is exploring combination therapy beyond lenalidomide, and next-generation sequencing may identify secondary mutations that could be an additional avenue for treatment.

KEYWORDS:

• MDS
• del(5q)
• high-risk
• lenalidomide
• TP53
• transplantation
• progression

Article Highlights

• Myelodysplastic syndrome is a heterogeneous group of hematological disorders that result from ineffective blood cell production and maturation.

• Disease phenotype often expresses chromosomal abnormalities, most commonly of which may include deletions of the long arm of chromosome 5.

• Outcomes with lenalidomide are less favorable in higher-risk patients with deletions of the long arm of chromosome 5 when compared with the lower-risk cohort.

• TP53 mutations predict poor outcomes to lenalidomide in higher-risk patients harboring a deletion 5q, while replacing therapy with hypomethylating agents may enhance response rates without improving survival.

• Emerging data and next-generation sequencing will explore combination therapies and additional mutational events that may impact prognosis and treatment.

Declaration of interest

S Gore is a consultant for Celgene and AbbVie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.