Abstract
Phosphoproteomic analysis reveals hyperactivation of mTOR/STAT3 and LCK/Calcineurin axes in pediatric early T-cell precursor ALL
Highlights
We analyzed bone marrow aspirates of 78 AIEOP (Italian Association of Pediatric Hematology and Oncology) T-ALL patients at diagnosis (16 Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) and 62 other T-ALLs of which 22 early-T, 31 thymic and 9 mature T-ALL defined as described in Supplementary Table S1, collected in the period September 2009–April 2014) through Reverse Phase Protein Arrays (RPPA)
No differences were observed between FLT3-mutated and non-mutated patients at the level of AKT/mTOR signaling. This may be due to the limited number of patients analyzed, these data allow to hypothesize that the high signaling observed in ETP-ALL has grounds other than the solely somatic mutations, in keeping with the observation that the AKT/mTOR hyperactivation is neither ascribable to the presence of PTEN mutations, nor can the JAK/ STAT pathway hyperactivation be associated to somatic mutations in IL7R, JAK1, JAK2 or JAK3 genes (Supplementary Table S3)
The activation of the Calcineurin-NFAT pathway was already demonstrated to be crucial for the maintenance of the T-cell leukemic phenotype in vivo,[11] and all these findings suggest that in ETP-ALL the upregulation of the LCK/Calcineurin pathway could contribute to leukemogenesis
Summary
Phosphoproteomic analysis reveals hyperactivation of mTOR/STAT3 and LCK/Calcineurin axes in pediatric early T-cell precursor ALL We analyzed bone marrow aspirates of 78 AIEOP (Italian Association of Pediatric Hematology and Oncology) T-ALL patients at diagnosis (16 ETP-ALL and 62 other T-ALLs of which 22 early-T, 31 thymic and 9 mature T-ALL defined as described in Supplementary Table S1, collected in the period September 2009–April 2014) through Reverse Phase Protein Arrays (RPPA).
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