To the editor

We read with great interest the recent paper by Bănescu et al1 addressing the association of copy number aberrations (CNAs) with European LeukemiaNet risk category, somatic mutations, clinical features, and overall survival in patients with acute myeloid leukemia (AML). The authors assessed the use of multiplex ligation–dependent probe amplification (MLPA) for analyzing the impact of CNAs on patient outcome. The presence of recurrent somatic mutations in the FLT3, NPM1, and DNMT3A genes was also assessed.1

Acute myeloid leukemia is a heterogenous disease characterized by expansion of undifferentiated myeloid precursor cells, leading to impaired hematopoiesis and normal bone marrow failure. Leukemia progenitor cells acquire recurrent genetic abnormalities and/or distinct somatic mutations, known as driver mutations, which is important in disease diagnosis and prognosis as well as impacts the efficacy of chemotherapy.2 Data on these abnormalities allow risk stratification and further precise classification of leukemia.3 Deletions, duplications, and other genomic rearrangements result in dosage imbalance of genes. The assessment of these relatively frequent abnormalities may increase our knowledge on the pathogenesis of AML. Copy number aberrations are detected using the gold standard array-based methods: comparative genomic hybridization and single nucleotide polymorphisms, while MLPA is a relatively new, cost-effective, accurate, and reliable technique for CNA detection.

Bănescu et al1 demonastrated an association between the presence of CNAs and adverse risk category in the European LeukemiaNet classification in patients with AML (P <0.0001). However, in the univariate Cox regression analysis, the presence of CNAs was not found to predict death in the study cohort. There were also no differences in the survival rate in patients with and without CNAs among those with somatic mutations in the FLT3, NPM1, and DNMT3A genes. However, the presence of CNAs was associated with the FLT3 D835 / FLT3TKD mutation (P = 0.02). A bidirectional interaction between CNAs and the Eastern Cooperative Oncologic Group Scale (ECOG) performance status was also found, which appears to be somewhat surprising. The presence of CNAs in patients with good performance (ECOG ≤2) was found to be associated with better outcome, while in patients in poor clinical condition (ECOG ≥3), it was connected with an increased risk of death. Generally, the presence of CNAs as a genomic instability marker is an important factor adversely affecting survival in cancer patients. Considering the results presented by Bănescu et al,1 it would be interesting to investigate how many CNAs were found and which genes were most frequently affected. The assessment of CNAs may be interesting in patients both with de novo and with relapsed AML. Furthermore, the longitudinal assessment of CNAs, both at diagnosis and in relapse, might expand our knowledge on AML chemosensitivity and clonal disease evolution.

Nowadays, next-generation sequencing (NGS) technology provides important data for optimization and personalization of AML treatment, and it becomes increasingly widely available. However, MLPA might be considered as a complementary tool to NGS. A recently described MLPA-based NGS technique uses MLPA products to construct a library that can be transferred into the NGS procedure. By using this approach, CNAs of target genes may be detected with improved precision on a large scale.4

In the study by Bănescu et al,1 complete remission was achieved in 15% of patients. According to a recent study on survival in patients with AML treated with standard intensive chemotherapy, remission may be achieved in 70% of patients with de novo AML younger than 60 years and in 50% of older patients, leading to a 5-year overall survival rate of 40% to 50% and 20% to 30% in younger and older patients, respectively.5 It is possible that if the authors added more clinical data regarding treatment modalities used in the study cohort, we would be able to better understand the impact of CNAs on risk assessment and outcome in patients with AML.