Clonal hematopoiesis of indeterminate potential–associated mutations and risk of comorbidities in patients with myelodysplastic syndrome

Kiran Naqvi, Koji Sasaki, Guillermo Montalban-Bravo, Ana Alfonso Pierola, Musa Yilmaz, Nicholas Short, Rita Assi, Elias Jabbour, Farhad Ravandi, Tapan Kadia, Sherry Pierce, Koichi Takahashi, Graciela Nogueras Gonzalez, Rashmi Kanagal-Shamanna, Keyur Patel, Kelly A. Soltysiak, Hagop M. Kantarjian, Guillermo Garcia-Manero

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2233-2241
Number of pages9
JournalCancer
Volume125
Issue number13
DOIs
StatePublished - Jul 1 2019

Keywords

  • clonal hematopoiesis of indeterminate potential
  • comorbidities
  • mutations
  • myelodysplastic syndromes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

MD Anderson CCSG core facilities

  • Biostatistics Resource Group
  • Clinical Trials Office

Fingerprint

Dive into the research topics of 'Clonal hematopoiesis of indeterminate potential–associated mutations and risk of comorbidities in patients with myelodysplastic syndrome'. Together they form a unique fingerprint.

Cite this