Banca de DEFESA: BRENNO VINICIUS MARTINS HENRIQUE

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : BRENNO VINICIUS MARTINS HENRIQUE
DATE: 03/10/2025
TIME: 09:00
LOCAL: Plataforma TEAMS
TITLE:

Screening and monitoring of GATA1 gene mutations in leukemogenesis associated with
Down syndrome

 

KEY WORDS:

Myeloid leukemia, Down syndrome, GATA1, mutation, minimal residual disease.

PAGES: 52
BIG AREA: Ciências Biológicas
AREA: Imunologia
SUMMARY:

Introduction: Children with Down syndrome are more likely to develop hematologic malignancies and, in some cases, may develop a rare and specific myeloid leukemia (MLDS). In addition to other biological events, trisomy of chromosome 21 together with mutations in exons 2 and 3 of the hematopoietic transcription factor GATA-1 trigger abnormal cell proliferation. It is known that GATA-1 mutations disrupt the abundance of the full-length GATA-1 protein, leading to an elevated expression level of a truncated isoform (GATA1s). Although these mutations are most likely to occur in exons 2 and 3, they can appear in different forms, including substitutions, duplications, or deletions. Thus, these molecular changes can be used as molecular targets to identify malignant cells in the diagnosis or recurrence of the disease. Methods: In this study, we leveraged this molecular landscape, based on the detection of specific mutations, to monitor patients diagnosed with ML-DS who underwent therapeutic regimens. Results: In our sample series, sequencing analyses revealed a total of 58 different mutations, mainly distributed in regions flanking exons 2 and 3, with a predominance in exon 2, which is characteristic for LM-SD cases. Among the identified mutations, 66.7% (n=39) correspond to insertions or deletions (Indels), which promote the loss of expression of the long isoform of the GATA1 gene and can thus be classified as pathogenic in the LM-SD context. No variant was described in more than one patient, highlighting the diversity of changes that can occur in the GATA1 gene. As the cohort was mostly composed of individuals with suspected TAM or LM-SD, as expected, this was the most frequent type of alteration. Additionally, 21.0% (n=12) of the mutations are duplications, while 12.3% (n=7) are SNVs (Single Nucleotide Variations). These data indicate a diversity of genetic alterations in the GATA1 gene, with a predominance of indels, which may have important implications for gene functionality and the development of associated diseases. Conclusions: Throughout this study, we were able to gather important information about mutations in the GATA1 gene in children with Down syndrome, but many aspects still need to be better understood. One of the main challenges we faced was the significant number of variants classified as of uncertain significance.

COMMITTEE MEMBERS:
Externa ao Programa - 2088007 - CARLA NUNES DE ARAUJO - nullPresidente - 2676451 - CIRO MARTINS GOMES
Externo à Instituição - FABIANO JOSE QUEIROZ COSTA - HUB
Externo à Instituição - KLEYTON DE CARVALHO MESQUITA - TRT10