Research Article
American Journal of BioMedicine
Volume 12, Issue 3, 2024, Pages 67- 82 
10.18081/2333-5106/2024.12/67
Daniela Landon, 
, M Azoicăi , V SoRelle 1 *
Received 22 May 2023; revised 09 July 2024; accepted 21 July 2024; published 15 August 2024
Abstract
The objective of this study was to evaluate the most important gene and miRNA mutations involved in the development of acute lymphoblastic leukaemia (ALL) in Romania and their potential to serve as patients’ prognostic biomarkers of early response to therapy and treatment outcome. A comparative analysis was performed to evaluate the susceptibility to ALL in the context of genetic factors such as somatic mutations and gene expression mutations in B-cell precursor (BCP) ALL. To achieve this aim, a retrospective study involving 73 Romanian BCP ALL patients was conducted, and the influence of genetic defects on basic clinical and immune-phenotypic characteristics was evaluated. The presence of mutations in FLT3, NRAS, PIK3CA, and KMT2A genes and their combinations were tested for associations with clinical parameters and the influence on the overall survival (OS) and event-free survival (EFS) of BCP ALL Romanian patients after therapy initiation. Gene expression profiling for the miRNA genes miR-18b, miR-19b, miR-222, and miR-423-5p and their influence on the OS and EFS of 48 BCP ALL Romanian patients were evaluated. The cumulative results suggest that the point mutations C1543T (pro537ser in the Flt3 receptor protein, rs786202394) and G3-4A (rs786202383) in the tyrosine kinase domain of the Flt3 receptor, and the somatic mutation c.64C>G in the codon 22 of the KMT2A gene may play a role in the susceptibility of Romanian patients with BCP ALL to develop the disease, affecting the prognosis of the patients. Unexpectedly, the negative prognosis of the mutation C1543T (pro537ser) in the Flt3 receptor protein was correlated with the good response to therapy and considered a favourable marker. Gene expression profiling analysis indicated that low expression levels of miR-223.3p and miR-222-3p could serve as adverse prognostic factors in BCP ALL, representing possible targets for therapy. In conclusion, this is the first study performed on the Romanian population that evaluates the influence of gene and miRNA mutations on the occurrence and prognosis of BCP ALL.
Keywords: Acute lymphoblastic leukaemia (ALL); Flt3 receptor protein; BCP ALL
Copyright © 2024 SoRelle, et al. This article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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