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- 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; Terra-Granado, Eugênia; Pombo-de-Oliveira, Maria S.; da Paz Zampier, Carolina; Mansur, Marcela B.; da Conceição Barbosa, Thayana; Chagas Neto, Paulo; Dallapicola Brisson, Gisele; dos Santos Bueno, Filipe Vicente; Cezar Sardou, Ingrid; Gonçalves Aguiar, Bruno; Silva Dias, Anna Carolina; Pedral Sampaio, Geraldo; Antônio Gomes Oliveira, Raimundo; de Oliveira, Claudia Teresa; Casagranda, Cesar; Ramos Vera, Geni
- 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/B del (71.4%), NOTCH1 mut (47.6%) and FBXW7 mut (17%). ETP-ALL had frequent FLT3 mut (22.2%) and SUZ12 del (16.7%) (p < 0.001), while CDKN2A/B del were rarely found in this subtype (p < 0.001). The early cortical T-ALL subtype had high frequencies of NOTCH1 mut and IL7R mut (71%, 28.6%, respectively), whereas, mature T-ALL with double positive CD4/CD8 had the highest frequencies of STIL-TAL1 (36.7%), LEF1 del (27.3%) and CASP8AP2 del (22.7%). The co-existence of two groups of T-ALL with NOTCH1 mut /IL7R mut, and with TLX3/SUZ12 del /NF1 del/ IL7R mut, were characterized with statistical significance (p < 0.05) but only STIL-TAL1 (pOS 47.5%) and NOTCH1 WT/ FBXW7 WT (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.
- Subjects
GENOTYPES; T cells; LYMPHOBLASTIC leukemia; POLYMERASE chain reaction; FLOW cytometry
- Publication
Frontiers in Oncology, 2019, pN.PAG
- ISSN
2234-943X
- Publication type
Article
- DOI
10.3389/fonc.2019.00316