TY - JOUR
T1 - Clonal hematopoiesis of indeterminate potential–associated mutations and risk of comorbidities in patients with myelodysplastic syndrome
AU - Naqvi, Kiran
AU - Sasaki, Koji
AU - Montalban-Bravo, Guillermo
AU - Alfonso Pierola, Ana
AU - Yilmaz, Musa
AU - Short, Nicholas
AU - Assi, Rita
AU - Jabbour, Elias
AU - Ravandi, Farhad
AU - Kadia, Tapan
AU - Pierce, Sherry
AU - Takahashi, Koichi
AU - Nogueras Gonzalez, Graciela
AU - Kanagal-Shamanna, Rashmi
AU - Patel, Keyur
AU - Soltysiak, Kelly A.
AU - Kantarjian, Hagop M.
AU - Garcia-Manero, Guillermo
N1 - Funding Information:
This work was supported in part by The University of Texas MD Anderson Cancer Center Support Grant (CA016672), The University of Texas MD Anderson MDS/AML Moon Shot, and Leukemia Texas.
Publisher Copyright:
© 2019 American Cancer Society
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
KW - clonal hematopoiesis of indeterminate potential
KW - comorbidities
KW - mutations
KW - myelodysplastic syndromes
UR - http://www.scopus.com/inward/record.url?scp=85062937744&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062937744&partnerID=8YFLogxK
U2 - 10.1002/cncr.32056
DO - 10.1002/cncr.32056
M3 - Article
C2 - 30861111
AN - SCOPUS:85062937744
SN - 0008-543X
VL - 125
SP - 2233
EP - 2241
JO - Cancer
JF - Cancer
IS - 13
ER -