Key result
In patients with MDS, DNMT3A and JAK2 mutations were associated with higher likelihoods of prior myocardial infarction (OR 2.62; P=0.03) and veno-occlusive disease (OR 6.48; P=0.02), respectively.
Why the study?
CHIP-associated mutations increase atherosclerotic heart disease risk and comorbidities significantly impact MDS prognosis, but the association and impact of CHIP mutations on comorbidities in MDS patients remained to be determined.
Are CHIP-associated mutations associated with specific comorbidities in patients with myelodysplastic syndromes?
Cohort (n=566)
No
Are CHIP-associated mutations associated with specific comorbidities in patients with myelodysplastic syndromes?
Odds Ratio: 2.62
p-value: p=0.03
In patients with myelodysplastic syndromes, DNMT3A and JAK2 mutations are associated with a significantly higher likelihood of prior myocardial infarction and thrombotic events.
CHIP mutations associate with comorbidities like prior MI in MDS; leaves open independent prognostic value beyond existing scores.
BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP)-associated mutations increase the risk of atherosclerotic heart disease. Comorbidities significantly impact the prognosis of patients with myelodysplastic syndromes (MDS). The objective of this study was to determine the association and impact of CHIP mutations with comorbidities in patients with MDS. METHODS: This retrospective analysis of 566 consecutive patients with MDS was conducted at The University of Texas MD Anderson Cancer Center from August 2013 to December 2016. The 27-item Adult Comorbidity Evaluation (ACE-27) scale was used to assess the severity of comorbid conditions. Next-generation sequencing was used to detect the presence of CHIP mutations in bone marrow aspirates. Spearman correlations and logistic regression analyses were used to determine the association between mutations and comorbidities. RESULTS: Mutations in the genes tet methylcytosine dioxygenase 2 (TET2), ASXL transcriptional regulator 1 (ASXL1), DNA methyltransferase 3α (DNMT3A), Janus kinase 2 (JAK2), and tumor protein 53 (TP53) were noted in 20%, 18%, 9%, 2%, and 21% of patients, respectively. Patients with DNMT3A and JAK2 mutations had higher likelihoods of a prior history of myocardial infarction (odds ratio, 2.62; P = .03) and veno-occlusive disease (odds ratio, 6.48; P = .02), respectively. TP53 mutation was associated with a prior history of malignancy. Patients with TET2 mutation had no association with any comorbidity. A prognostic model including the revised International Prognostic Scoring System classification, the ACE-27 score, and TP53 mutation status (the I-RAT model) predicted median overall survival. CONCLUSIONS: In patients with MDS, the presence of CHIP-associated mutations is associated with comorbidities. DNMT3A and JAK2 mutations were associated with higher likelihoods of prior myocardial infarction and thrombotic events. There was no association between comorbidity and TET2 mutation. Incorporating the revised International Prognostic Scoring System classification with the ACE-27 and TP53 mutation status improved outcome prediction in patients with MDS.
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Naqvi et al. (2019) conducted a cohort in Myelodysplastic syndrome (n=566). CHIP-associated mutations vs. Absence of specific mutations was evaluated on Prior history of myocardial infarction (for DNMT3A mutation) (OR 2.62, p=0.03). In patients with MDS, DNMT3A and JAK2 mutations were associated with higher likelihoods of prior myocardial infarction (OR 2.62; P=0.03) and veno-occlusive disease (OR 6.48; P=0.02), respectively.
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