The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia

• Published in: Frontiers in oncology Vol. 9; p. 316
• Main Authors: Noronha, Elda Pereira, Marques, Luísa Vieira Codeço, Andrade, Francianne Gomes, Thuler, Luiz Claudio Santos, Terra-Granado, Eugênia, Pombo-de-Oliveira, Maria S
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 30-04-2019
• Subjects: childhood; early T-cell precursor acute lymphoblastic leukemia; immunophenotypic subtypes; molecular alterations; Oncology; overall survival; T-cell acute lymphoblastic leukemia; immunophenotypic subtypes; overall survival; early T-cell precursor acute lymphoblastic leukemia; childhood; T-cell acute lymphoblastic leukemia; molecular alterations
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2019.00316

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,
= 27), immature (
= 38), early cortical (
= 15), cortical (
= 50), late cortical (
= 53), CD4/CD8 double negative mature (
= 31), double positive mature (
= 35) and simple positive mature (
= 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
(71.4%),
(47.6%) and
(17%). ETP-ALL had frequent
(22.2%) and
(16.7%) (
< 0.001), while
were rarely found in this subtype (
< 0.001). The early cortical T-ALL subtype had high frequencies of
and
(71%, 28.6%, respectively), whereas, mature T-ALL with double positive CD4/CD8 had the highest frequencies of
(36.7%),
(27.3%) and
(22.7%). The co-existence of two groups of T-ALL with
, and with
/
, were characterized with statistical significance (
< 0.05) but only
(pOS 47.5%) and
/
(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
and
rearrangement had a prognostic impact, independent of immunophenotype.