Caracterização da Leucemia Mieloide Aguda com mutação FLT3-ITD

Abstract

Acute Myeloid Leukemia (AML) is a hematological malignancy characterized by clonal proliferation of myeloblasts in bone marrow, peripheral blood and other tissues. It is due to obtaining mutations that lead to the transformation of normal hematopoietic stem cells into leukemic ones. The FLT3 gene is a proto-oncogene of the receptor tyrosine kinase class, which regulates proliferation, differentiation and apoptosis. FLT3-ITD, is one of the main mutations related to the FLT3 gene, identified in 20 to 30% of individuals with AML. It acts on the juxtamembrane domain and causes insertions of a repeated sequence within the protein coding region. Thus, the diagnosis of the FLT3-ITD mutation is important in AML. A systematic review was carried out where 79 scientific articles, identified in the VHL, PubMed, SciELO and ScienceDirect databases, published between 2018 and 2023, in English and Spanish, were included in the study. There were a total of 2111 AML patients with FLT3-ITD mutation. A higher occurrence of FLT3-ITD mutation was observed in females. The age range ranged from 10 to 87 years, with a median between 47 and 67 years. The main sample types used in the studies were peripheral blood (4/9) and bone marrow aspirate (6/9). The most used molecular biology techniques were PCR and NGS. The karyotype was normal in 73.0% of the individuals, and, among the cited cytogenetic abnormalities, the following were highlighted: t(9:22); t(8:21); t(6:9); +8; inv16 and the complex karyotype. Concomitant mutations associated with FLT3-ITD included NPM1 (68.5%) and DNMT3A (31.5%). The characteristics of AML, with FLT3-ITD mutation, can help in the diagnosis, prognosis and treatment. It is necessary to carry out more studies that evaluate the relationship between the FLT3-ITD mutation and gender and age group, molecular diagnosis, cytogenetics and concomitant mutations, in addition to investigating intratumoral plurality.