RRML - FLT3-ITD DNA allelic burden, but not mRNA levels, influences the biological characteristics of AML patients

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Nr. 29(1)/2021 DOI:10.2478/rrlm-2021-0004

Research article

FLT3-ITD DNA allelic burden, but not mRNA levels, influences the biological characteristics of AML patients

Dan S Soare, Eugen Radu, Ion Dumitru, Aurora Arghir, Cristina Enache, Horia Bumbea, Ana M Vlădăreanu

Correspondence should be addressed to: Horia Bumbea

Abstract:

FMS-like tyrosine kinase 3 gene internal tandem (FLT3-ITD) mutations represent one of the most frequent genetic lesions in acute myeloid leukemia (AML) and imparts a negative prognostic. For an optimal patient management, current clinical guidelines recommend the evaluation of the allelic ratio (AR), expressed as the DNA FLT3-ITD/WT mutational burden. We sought to evaluate the differences between the AR and FLT3-ITD/WT mRNA ratio (RR) and their respective impact on the biological characteristics of AML patients. A total of 32 DNA and mRNA samples from AML patients with FLT3-ITD were evaluated. There was a good correlation between the AR and RR (Spearman’s rho= 0.652, P <0.001). None of the biological characteristics were influenced by the RR values, whereas patients with high AR values (≥0.5) had higher WBC counts (Mann-Whitney, P= 0.01), LDH levels (Mann-Whitney, P= 0.037), and circulating blasts levels (Mann-Whitney, P= 0.023) than patients with low AR values (<0.5). Also, there was a good correlation between AR values and WBC count (Spearman’s correlation, P= 0.001), and LDH levels (Spearman’s correlation, P= 0.007). In our study population the AR, but not the RR, influenced the biological characteristic of patients suggesting a dose-independent effect of FLT3-ITD mutations.

Keywords: acute myeloid leukemia, mRNA, FLT3-ITD, Allelic-ratio

Received: 1.10.2020
Accepted: 9.12.2020
Published: 2.1.2021

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Supplementary material

Soare DS, Radu E, Dumitru I, Arghir A, Enache C, Bumbea H, et al. FLT3-ITD DNA allelic burden, but not mRNA levels, influences the biological characteristics of AML patients. Rev Romana Med Lab. 2021;29(1):33-41. DOI:10.2478/rrlm-2021-0004