Banca de DEFESA: Fernanda Penna Lima Guedes de Amorim

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : Fernanda Penna Lima Guedes de Amorim
DATE: 23/09/2022
TIME: 14:00
LOCAL: auditório da Pós-Graduação da Faculdade de Medicina
TITLE:

Analysis of relative telomere length and investigation of chromosome abnormalities in patients with Myelofibrosis

 

KEY WORDS:

Myeloproliferative Neoplasms, Telomere Length, Myelofibrosis, Driver Mutations, JAK2, Chromosomal Microarray, Chromosome Rearrangements, Loss of Heterozygosis

PAGES: 91
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

Myelofibrosis (MF) is a rare chronic myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, inefficient hematopoiesis, and reduced survival. Driver mutations of JAK2, MPL or CALR genes are found in approximately 90% of patients, while the remaining 10% without driver mutations are termed “triple negative”. These driver mutations can be accompanied by other mutations, called cooperative mutations, such as RBI. Studies have indicated reduced telomere length in myelofibrosis, suggesting prognostic relevance for this biomarker. Furthermore, nowadays it is known that the genomic characterization of patients with myeloproliferative neoplasms (MPN) can lead to better diagnostic classification, prognostic assessment and treatment planning. The aims of the study were: 1) to investigate the relative length of the telomere (T/L) in MF-patients, 2) to analyze whether there is a relationship between the T/L and the existing type of driver mutation, sex and the International Prognostic Scoring System (IPSS), and 3) to perform chromosomal analysis by Microarray (CMA) and correlate the cytogenetic findings obtained by CMA with the median of overall survival. T/L was analyzed in peripheral blood samples from 36 MF-patients and 42 age-matched controls. T/L was determined by quantitative real-time PCR. Significant reduction in relative telomere length was observed among MF-patients compared to the control group. The T/L of patients with JAK2V617F positive mutation and JAK2V617F negative mutation was significantly reduced in both groups when compared to controls. Results from the present study showed that T/L is reduced in MF-patients, regardless of the presence of the JAK2V617F driver mutation. CMA showed that seventy-six percent of patients had regions of chromosomal gain or loss or areas of heterozygous loss. Patients who had a lower median survival (3.7 months) had chromosomal alterations that harbored tumor suppressor genes (NF1, RBI, TP53, DNMT3A, PPM1D). The present study suggests a possibility of better prognostic characterization of patients with myelofibrosis through th incorporation chromosomal microarray results in the prognostic scores.

BANKING MEMBERS:
Externo à Instituição - SHÉLIDA VASCONCELOS BRAZ - UNICESP
Interna - 2255360 - DORALINA DO AMARAL RABELLO RAMOS
Externo à Instituição - JOSE CARLOS MARTINS CORDOBA - HCB
Presidente - 2731816 - JULIANA FORTE MAZZEU DE ARAUJO