TY - JOUR
T1 - IGHV-associated methylation signatures more accurately predict clinical outcomes of chronic lymphocytic leukemia patients than IGHV mutation load
AU - Hussmann, Dianna
AU - Starnawska, Anna
AU - Kristensen, Louise
AU - Daugaard, Iben
AU - Thomsen, Astrid
AU - Kjeldsen, Tina E.
AU - Hansen, Christine Søholm
AU - Bybjerg-Grauholm, Jonas
AU - Johansen, Karina Dalsgaard
AU - Ludvigsen, Maja
AU - Kristensen, Thomas
AU - Larsen, Thomas Stauffer
AU - Møller, Michael Boe
AU - Nyvold, Charlotte Guldborg
AU - Hansen, Lise Lotte
AU - Wojdacz, Tomasz K.
N1 - Publisher Copyright:
© 2022 Ferrata Storti Foundation.
PY - 2022/4
Y1 - 2022/4
N2 - Currently, no molecular biomarker indices are used in standard care to make treatment decisions at diagnosis of chronic lymphocytic leukemia (CLL). We used Infinium MethylationEPIC array data from diagnostic blood samples of 114 CLL patients and developed a procedure to stratify patients based on methylation signatures associated with mutation load of the IGHV gene. This procedure allowed us to predict the time to treatment with a hazard ratio (HR) of 8.34 (95% confidence interval [CI]: 4.54-15.30), as opposed to a HR of 4.35 (95% CI: 2.60-7.28) using IGHV mutation status. Detailed evaluation of 17 cases for which the two classification procedures gave discrepant results showed that these cases were incorrectly classified using IGHV status. Moreover, methylation-based classification stratified patients with different overall survival (HR=1.82; 95% CI: 1.07-3.09), which was not possible using IGHV status. Furthermore, we assessed the performance of the developed classification procedure using published HumanMethylation450 array data for 159 patients for whom information on time to treatment, overall survival and relapse was available. Despite 450K array methylation data not containing all the biomarkers used in our classification procedure, methylation signatures again stratified patients with significantly better accuracy than did IGHV mutation load regarding all available clinical outcomes. Thus, stratification using IGHV-associated methylation signatures may provide better prognostic power than IGHV mutation status.
AB - Currently, no molecular biomarker indices are used in standard care to make treatment decisions at diagnosis of chronic lymphocytic leukemia (CLL). We used Infinium MethylationEPIC array data from diagnostic blood samples of 114 CLL patients and developed a procedure to stratify patients based on methylation signatures associated with mutation load of the IGHV gene. This procedure allowed us to predict the time to treatment with a hazard ratio (HR) of 8.34 (95% confidence interval [CI]: 4.54-15.30), as opposed to a HR of 4.35 (95% CI: 2.60-7.28) using IGHV mutation status. Detailed evaluation of 17 cases for which the two classification procedures gave discrepant results showed that these cases were incorrectly classified using IGHV status. Moreover, methylation-based classification stratified patients with different overall survival (HR=1.82; 95% CI: 1.07-3.09), which was not possible using IGHV status. Furthermore, we assessed the performance of the developed classification procedure using published HumanMethylation450 array data for 159 patients for whom information on time to treatment, overall survival and relapse was available. Despite 450K array methylation data not containing all the biomarkers used in our classification procedure, methylation signatures again stratified patients with significantly better accuracy than did IGHV mutation load regarding all available clinical outcomes. Thus, stratification using IGHV-associated methylation signatures may provide better prognostic power than IGHV mutation status.
UR - http://www.scopus.com/inward/record.url?scp=85123163113&partnerID=8YFLogxK
U2 - 10.3324/haematol.2021.278477
DO - 10.3324/haematol.2021.278477
M3 - Article
C2 - 34092057
AN - SCOPUS:85123163113
SN - 0390-6078
VL - 107
SP - 877
EP - 886
JO - Haematologica
JF - Haematologica
IS - 4
ER -