Please use this identifier to cite or link to this item: https://ninho.inca.gov.br/jspui/handle/123456789/11798
Title: The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia
Authors: Noronha, Elda Pereira
Marques, Luísa Vieira Codeço
Andrade, Francianne Gomes
Thuler, Luiz Claudio Santos
Pina, Eugênia Terra Granado
Oliveira, Maria do Socorro Pombo de
Keywords: Leucemia-Linfoma Linfoblástico de Células T Precursoras
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Criança
Child
Imunofenotipagem
Immunophenotyping
subtypes
molecular alterations
Leucemia-Linfoma Linfoblástico de Células Precursoras
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Sobrevida
Survival
Overall
Issue Date: 2019
Publisher: Frontiers in oncology
Citation: NORONHA, Elda Pereira et al. The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia. Frontiers in oncology, v. 316, n. 9, p. 1-10, apr. 2019.
Abstract: T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous malignancy, which reflects distinctive stages of T-cell differentiation arrest. We have revisited a cohort of pediatric T-ALL, in order to test if immunophenotypes associated with molecular alterations would predict the patient’s outcome. Genetic mutations, translocations and copy number alterations were identified through Sanger sequencing, RT-PCR, FISH and multiplex ligation-dependent probe amplification (MLPA). We defined 8 immunophenotypic T-ALL subtypes through multiparametric flow cytometry: early T-cell precursor (ETP, n = 27), immature (n = 38), early cortical (n = 15), cortical (n = 50), late cortical (n = 53), CD4/CD8 double negative mature (n = 31), double positive mature (n = 35) and simple positive mature (n = 31) T-ALL. Deletions (del) or amplifications (amp) in at least one gene were observed in 87% of cases. The most frequent gene alterations were CDKN2A/Bdel (71.4%), NOTCH1mut (47.6%) and FBXW7mut (17%). ETP-ALL had frequent FLT3mut (22.2%) and SUZ12del (16.7%) (p < 0.001), while CDKN2A/Bdel were rarely found in this subtype (p < 0.001). The early cortical T-ALL subtype had high frequencies of NOTCH1mut and IL7Rmut (71%, 28.6%, respectively), whereas, mature T-ALL with double positive CD4/CD8 had the highest frequencies of STIL-TAL1 (36.7%), LEF1del (27.3%) and CASP8AP2del (22.7%). The co-existence of two groups of T-ALL with NOTCH1mut/IL7Rmut, and with TLX3/SUZ12del/NF1del/IL7Rmut , were characterized with statistical significance (p < 0.05) but only STIL-TAL1 (pOS 47.5%) and NOTCH1WT/FBXW7WT (pOS 55.3%) are predictors of poor T-ALL outcomes. In conclusion, we have observed that 8 T-ALL subgroups are characterized by distinct molecular profiles. The mutations in NOTCH1/FBXW7 and STIL-TAL1 rearrangement had a prognostic impact, independent of immunophenotype.
Description: p. 1-10.: il. color. e p&b.
URI: https://ninho.inca.gov.br/jspui/handle/123456789/11798
ISSN: 2234-943X
Appears in Collections:Artigos de Periódicos da área de Pediatria



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