Full text
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| Author(s): |
Guilherme Navarro Nilo Giusti
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2019-02-22 |
| Examining board members: |
José Andrés Yunes;
Márcio José da Silva;
Juliana Godoy Assumpção
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| Advisor: | José Andrés Yunes |
| Abstract | |
Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children. The current childhood ALL treatment protocols achieve disease-free survival rates close to 90%. Part of this success is due to the allocation of patients in different risk groups, according to prognostic factors assessed during the treatment. Initial treatment response, assessed by the quantification of the patient¿s residual leukemic cells, or Minimal Residual Disease (MRD), is one of the most important factors to identify these risk groups. The protocol of the Brazilian Group for the treatment of ALL (GBTLI LLA-2009) uses MRD at days 15 and 35, evaluated by flow cytometry and qPCR respectively, to allocate the patients into groups for different chemotherapy treatment schemes. Flow cytometry and qPCR MRD assessment are expensive, require a lot of experience from the analyst and demand immediate analysis (cytometry) or a multistep 25 days-long analysis (qPCR). These factors hamper these methods¿ broad utilization in Brazil. The number of children in the country who are able to take advantage of the MRD exam is 100 a year (3,2% of total pediatric ALL cases in our country). In this Project, we standardized MRD assessment in childhood ALL by Next Generation Sequencing of IgH rearrangements. This assay is faster than the conventional ones and has high scalability potential. Once standardized, this method was validated using pediatric pre-B ALL samples previously analyzed at Centro Infantil Boldrini. The NGS MRD results were compared to the qPCR MRD ones, achieving a result satisfaction rate of 88,5% and a Pearson correlation coefficient of 0,86. The next steps are to keep polishing the method, by increasing its sensitivity and accuracy, adding additional established pediatric pre-B ALL markers to the protocol and adapting the method for other types of leukemia (AU) | |
| FAPESP's process: | 17/03942-8 - Quantification of minimal residual disease in acute lymphoblastic leukemia by high throughput sequencing |
| Grantee: | Guilherme Navarro Nilo Giusti |
| Support Opportunities: | Scholarships in Brazil - Master |