Authors’ reply
We would like to thank Mensah-Glanowska et al1 for their interest in our recently published article regarding the multiplex ligation-dependent probe amplification (MLPA) utility in patients with acute myeloid leukemia (AML)2 and also for their constructive comments.
We agree with the authors that the MLPA-based next-generation sequencing (NGS) technology is a useful method that provides important data for optimization and personalization of AML treatment. We have to mention that for low and middle-income countries, it may be very difficult to support the cost of MLPA-based NGS analysis. The cost of such analysis is lower if the analysis includes a large number of patients, while for 1 to 20 patients, for example, the cost is increased. At the same time, the analysis report for such patients had to be ready as soon as possible, for optimization and personalization of AML treatment. Currently, we are also investigating our AML patients by NGS analysis, trough research grants, but for financial reasons, we perform NGS analysis only when we have more AML samples to be included in each run (Ion PI chip). Unfortunately, in this situation it may be too late for some patients with AML.
Regarding the MLPA technique, we agreed that it had several limitations, but it is useful for the fast investigation of patients with AML at a low cost. In our study, we did not analyze separately our copy number aberrations (CNAs) due to the increased type of different CNAs. As we mentioned, 283 adult patients with AML were evaluated for CNAs and they were found in 90 (31.8%) cases (64 cases with 1 CNA, 11 cases with 2 CNAs, 15 cases with ≥3 CNAs).
Briefly, 6 cases with 17p or 17q deletion (TP53, IKZF3, UNC13D genes); 10 with CNAs for 5q, especially 5q33 (EBF1, MIR145, MIR146A genes), 12 with CNAs represented by deletions of 7p (IKZF1) or 7q (MET, DPP6, RELN), 5 with CNAs for 9p21.3 and 9p13.2 (MTAP, CDKN2A, CDKN2B, PAX5 genes), 6 with CNAs for 2p24.3 and 2p23.2 (MYCN, ALK genes), 6 patients with CNAs for 8q24.21 (MYC gene), 3 with CNAs for 13q14 (RB1, MIR15A, DLEU2, DLEU1 genes), 7 with CNAs on X chromosome, 2 with CNAs for 3p26.3 (GHL1-5 gene), 2 with CNAs for 21q22 (RUNX1 gene), 2 with CNAs for 21q11(HSPA13 gene), 1 with CNAs for 10q23.31 (PTEN gene), 2 with CNAs for 12p13 (ETV6, CCND2, MDM2 genes), etc. As it may seem, we identified an increased number of different types of CNAs. Considering the relatively small number of cases for each type of CNA, which was not sufficient to ensure the power of statistical analysis separately on each CNA, we were unable to perform statistical analysis for each CNA. Taking into account that AML is characterized by chromosomal abnormalities (including also translocations) and gene mutations, we recommend the use of MLPA analysis in addition to other cytogenetic and molecular techniques for AML patient investigation.
Our MLPA results presented in the paper are general and must be clinically interpreted with caution. The main objective of the mentioned paper was to assess the utility of a multiplex ligation–dependent probe amplification (MLPA) assay in AML. As it was already mentioned,1-3 we consider MLPA- and NGS-based techniques useful in the diagnosis of patients with AML due to the clinical impact of the genetic anomalies in AML, but also for precision medicine in AML. Besides, several molecular techniques can be useful in the diagnosis of patients with AML, each of them covering the limits of the other technique.3
Regarding the complete remission, it was considered achieved in 15% of our patients while in the study by Medeiros et al,4 it is estimated that the remission may be achieved in 50% of older AML cases (>60 years). The discrepancies in the results may be explained by the fact that those cases with relapse after complete or partial remission were included in the relapse group. Moreover, we did not subcategorize our patients according to their age. Treatment modalities used in our patients were the standard ones, according to the patient’s age and comorbidities, with a low or high dose of so-called 2+3 or 7+3 regimens5 or a high dose with hematopoietic stem cell transplantation.
Florin Tripon, MD, PhD, Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 38 Gh Marinescu St, 540 139, Târgu Mureș, Romania, phone: +40 265215551, email: tripon.florin.2010@gmail.com
April 30, 2020.
Claudia Bănescu, Florin Tripon, Adrian P. Trifa, Andrei G. Crauciuc, Alina Bogliș, Erzsebet Lazar, Delia Dima, Ioan Macarie, Carmen Duicu, Mihaela Iancu (CB, FT, and AB: Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureș, Romania; FT, AGC, and AB: Department of Medical Genetics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureș, Romania; APT: Department of Medical Genetics, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj‐Napoca, Cluj‐Napoca, Romania; EL and IM: Department of Internal Medicine, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureș, Romania; DD: Department of Hematology, The Oncology Institute “Prof. Dr. I. Chiricuța,” Cluj‐Napoca, Cluj‐Napoca, Romania; CD: Department of Clinical Science, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureș, Romania; MI: Department of Medical Informatics and Biostatistics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj‐Napoca, Cluj‐Napoca, Romania)
None declared.
Bănescu C, Tripon F, Trifa AP, et al. Presence of copy number aberrations and clinical prognostic factors in patients with acute myeloid leukemia: an analysis of effect modification. Authors’ reply. Pol Arch Intern Med. 2020; 130: 347-348. doi:10.20452/pamw.15327
- 1.
- Mensah-Glanowska P, Magda P, Sacha T. Presence of copy number aberration and clinical prognostic factors in patients with acute myeloid leukemia: an analysis of effect modification. Pol Arch Intern Med. 2020; 130: 346-347.Crossref
- 2.
- Bănescu C, Tripon F, Trifa AP, et al. Presence of copy number aberration and clinical prognostic factors in patients with acute myeloid leukemia: an analysis of effect modification. Pol Arch Intern Med. 2019; 129: 898-906.Crossref
- 3.
- Tripon F, Crauciuc GA, Moldovan VG, et al. Simultaneous FLT3, NPM1 and DNMT3A mutations in adult patients with acute myeloid leukemia – case study. Rev Romana Med Lab. 2019; 27: 245-254.Crossref
- 4.
- Medeiros BC, Chan SM, Daver NG, et al. Optimizing survival outcomes with post-remission therapy in acute myeloid leukemia. Am J Hematol. 2019; 94: 803-811.Crossref
- 5.
- American Cancer Society. Typical Treatment of Acute Myeloid Leukemia (Except APL). https://www.cancer.org/cancer/acute-myeloid-leukemia/treating/typical-treatment-of-aml.html. Accessed April 1, 2020.