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.

Details

Title
High expression of HMGA2 independently predicts poor clinical outcomes in acute myeloid leukemia
Author
Marquis, Miriam 1 ; Beaubois, Cyrielle 1 ; Vincent-Philippe Lavallée 2   VIAFID ORCID Logo  ; Abrahamowicz, Michal 3 ; Danieli, Coraline 3 ; Lemieux, Sébastien 4   VIAFID ORCID Logo  ; Ahmad, Imran 5 ; Wei, Andrew 6 ; Ting, Stephen B 7 ; Fleming, Shaun 8 ; Schwarer, Anthony 9 ; Grimwade, David 10 ; Grey, William 11   VIAFID ORCID Logo  ; Hills, Robert K 12 ; Vyas, Paresh 13 ; Russell, Nigel 14 ; Sauvageau, Guy 15 ; Hébert, Josée 15 

1  The Quebec Leukemia Cell Bank, Research Centre, Maisonneuve-Rosemont Hospital, Montréal, Canada; The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Canada 
2  The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Canada; Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, Canada 
3  Epidemiology and Biostatistics Department, McGill University, Montréal, Canada 
4  The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Canada; Department of Computer Science and Operations Research, Université de Montréal, Montréal, Canada 
5  Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, Canada; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, Canada 
6  Department of Haematology, Alfred Hospital, Melbourne, Australia; Australian Centre for Blood Diseases, Monash University, Melbourne, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia 
7  Australian Centre for Blood Diseases, Monash University, Melbourne, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia; Department of Haematology, Eastern Health, Box Hill Hospital, Melbourne, Australia 
8  Department of Haematology, Alfred Hospital, Melbourne, Australia 
9  Department of Haematology, Eastern Health, Box Hill Hospital, Melbourne, Australia 
10  Cancer Genetics Laboratory, Department of Medical and Molecular Genetics, King’s College London, London, UK; UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group, Cardiff, UK 
11  Cancer Genetics Laboratory, Department of Medical and Molecular Genetics, King’s College London, London, UK 
12  UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group, Cardiff, UK; Centre for Trials Research, Cardiff University School of Medicine, Cardiff, UK 
13  MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine and Department of Haematology, University of Oxford and Oxford University Hospitals NHS Trust, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK 
14  UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group, Cardiff, UK; Centre for Clinical Haematology, Nottingham University Hospital (City Hospital Campus), Nottingham, UK 
15  The Quebec Leukemia Cell Bank, Research Centre, Maisonneuve-Rosemont Hospital, Montréal, Canada; The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Canada; Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, Canada; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, Canada 
Pages
1-12
Publication year
2018
Publication date
Jul 2018
Publisher
Springer Nature B.V.
e-ISSN
20445385
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41408-018-0103-6
ProQuest document ID
2079933504
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.