High expression of HMGA2 independently predicts poor clinical outcomes in acute myeloid leukemia

Miriam Marquis, Cyrielle Beaubois, Vincent Philippe Lavallée, Michal Abrahamowicz, Coraline Danieli, Sébastien Lemieux, Imran Ahmad, Andrew Wei, Stephen B. Ting, Shaun Fleming, Anthony Schwarer, David Grimwade, William Grey, Robert K. Hills, Paresh Vyas, Nigel Russell, Guy Sauvageau, Josée Hébert

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15 Citations (Scopus)

Abstract

In acute myeloid leukemia (AML), risk stratification based on cytogenetics and mutation profiling is essential but remains insufficient to select the optimal therapy. Accurate biomarkers are needed to improve prognostic assessment. We analyzed RNA sequencing and survival data of 430 AML patients and identified HMGA2 as a novel prognostic marker. We validated a quantitative PCR test to study the association of HMGA2 expression with clinical outcomes in 358 AML samples. In this training cohort, HMGA2 was highly expressed in 22.3% of AML, mostly in patients with intermediate or adverse cytogenetics. High expression levels of HMGA2 (H +) were associated with a lower frequency of complete remission (58.8% vs 83.4%, P < 0.001), worse 3-year overall survival (OS, 13.2% vs 43.5%, P < 0.001) and relapse-free survival (RFS, 10.8% vs 44.2%, P < 0.001). A positive HMGA2 test also identified a subgroup of patients unresponsive to standard treatments. Multivariable analyses showed that H + was independently associated with significantly worse OS and RFS, including in the intermediate cytogenetic risk category. These associations were confirmed in a validation cohort of 260 patient samples from the UK NCRI AML17 trial. The HMGA2 test could be implemented in clinical trials developing novel therapeutic strategies for high-risk AML.

Original languageEnglish
Article number68
Number of pages12
JournalBlood Cancer Journal
Volume8
Issue number8
DOIs
Publication statusPublished - 1 Aug 2018

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