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Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies
Published on: November 10, 2023
Genomic landscape of myelodysplastic/myeloproliferative neoplasm can predict response to hypomethylating agent
Theodoros Karantanos1, Hua-Ling Tsai2, Lukasz P Gondek1
1Division of Hematological Malignancies and Bone Marrow Transplantation, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Abstract:
There are currently no known predictors of myelodysplastic syndrome (MDS)/myeloproliferative overlap neoplasm (MPN) patients' response to hypomethylating agents (HMA). Forty-three patients with MDS/MPN who were treated with HMA during chronic phase and had next-generation sequencing using the established 63-genes panel were identified. Complete and partial remission and marrow response were assessed based on the MDS/MPN International Working Group response criteria. On univariate analysis, younger age, higher number of mutations, and mutations in SETBP1, RUNX1, or EZH2 were associated with no response. Multivariable analysis for modeling response were conducted via least absolute shrinkage and selection operator logistic regression approach, and showed that mutations in SETBP1, RUNX1, or EZH2 predict lack of HMA response. While limited by sample size, our findings suggest that genomic landscape can potentially identify MDS/MPN patients with lower likelihood of response to HMA.
Insights
Predicting response to hypomethylating agents (HMA) in myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) is challenging. Genomic mutations in SETBP1, RUNX1, or EZH2 may indicate a lack of response to HMA therapy.
Area of Science:
- Hematology
- Genomics
- Oncology
Background:
- Predicting treatment response in myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) remains a clinical challenge.
- Hypomethylating agents (HMA) are a standard treatment, but patient response varies significantly.
- No established biomarkers currently predict HMA efficacy in MDS/MPN patients.
Purpose of the Study:
- To identify predictors of response to hypomethylating agents (HMA) in patients with MDS/MPN.
- To investigate the association between specific gene mutations and HMA treatment outcomes.
- To explore the potential of genomic profiling for stratifying MDS/MPN patients for HMA therapy.
Main Methods:
- Retrospective analysis of 43 MDS/MPN patients treated with HMA in chronic phase.
- Next-generation sequencing using a 63-gene panel was performed on patient samples.
- Response assessment based on International Working Group criteria; statistical analysis using logistic regression.
Main Results:
- Univariate analysis indicated younger age, higher mutation burden, and mutations in SETBP1, RUNX1, or EZH2 were associated with no response.
- Multivariable analysis confirmed that mutations in SETBP1, RUNX1, or EZH2 are independent predictors of lack of HMA response.
- These genomic alterations suggest a potential for identifying patients unlikely to benefit from HMA.
Conclusions:
- Genomic landscape, specifically mutations in SETBP1, RUNX1, or EZH2, may predict poor response to HMA in MDS/MPN.
- These findings highlight the potential utility of genetic profiling in guiding HMA treatment decisions.
- Further validation in larger cohorts is warranted to confirm these predictive biomarkers.
