Abstract
Objective:PTEN/AKT pathway deregulations have been reported to be associated with treatment response in acute leukemia. This study examined pediatric T-cell acute lymphoblastic leukemia (T-ALL) samples for PTEN and AKT1 gene variations and evaluated the clinical findings.Materials and Methods:Fifty diagnostic bone marrow samples of childhood T-ALL cases were investigated for the hotspot regions of the PTEN and AKT1 genes by targeted next-generation sequencing.Results:A total of five PTEN variations were found in three of the 50 T-ALL cases (6%). Three of the PTEN variations were first reported in this study. Furthermore, one patient clearly had two different mutant clones for PTEN. Two intronic single-nucleotide variations were found in AKT1 and none of the patients carried pathogenic AKT1 variations.Conclusion:Targeted deep sequencing allowed us to detect both low-level variations and clonal diversity. Low-level PTEN/AKT1 variation frequency makes it harder to investigate the clinical associations of the variants. On the other hand, characterization of the PTEN/AKT signaling members is important for improving case-specific therapeutic strategies.
Highlights
One of the key signal transduction pathways involved in malignant transformation is the PTEN/PI3K/AKT pathway, which regulates cellular metabolism, cell growth, translation, chromosome stability, and cell survival [1]
A total of 50 childhood T-cell acute lymphoblastic leukemia (T-ALL) patients were screened for hotspot regions of PTEN and AKT1 by targeted deep sequencing
A total of five PTEN variations were found in three of the 50 T-ALL cases (6%) and all the variations occurred in exon 7, truncating PTEN in the C2-domain
Summary
One of the key signal transduction pathways involved in malignant transformation is the PTEN/PI3K/AKT pathway, which regulates cellular metabolism, cell growth, translation, chromosome stability, and cell survival [1]. Survival factors can suppress apoptosis in a transcriptionindependent manner by activating the serine/threonine kinase AKT1, which phosphorylates and inactivates components of the apoptotic machinery [4]. PTEN as a tumor suppressor is frequently mutated in cancers and its inactivation results in constitutive activation of the PI3K/AKT pathway. PTEN/AKT abnormalities resulting in deletion, insertion, or missense mutations lead to differential regulation in different hematologic malignancies [10,11,12,13,14]. Genomic resequencing results showed that PI3K/AKT pathway genes are commonly mutated in pediatric and young adult T-cell acute lymphoblastic leukemia (T-ALL) cases [11,15]. PTEN and AKT1 variations and their clinical associations were analyzed in a group of childhood T-ALL cases
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Turkish journal of haematology : official journal of Turkish Society of Haematology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
