Advantages and Limitations of SNP Array in the Molecular Characterization of Pediatric T-Cell Acute Lymphoblastic Leukemia.

Monika Lejman,Katarzyna Skonieczka,Łukasz Sędek,Agata Pastorczak,Wojciech Młynarski,Jerzy R Kowalczyk,Joanna Zawitkowska,Joanna Taha,Tomasz Szczepański,Borys Styka,Marcin Braun,Monika Włodarczyk,Olga Haus

doi:10.3389/fonc.2020.01184

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a highly heterogeneous disease, and numerous genetic aberrations in the leukemic genome are responsible for the biological and clinical differences among particular ALL subtypes. However, there is limited knowledge regarding the association of whole-genome copy number abnormalities (CNAs) in childhood T-ALL with the course of leukemia and its outcome. The aim of this study was to identify the pattern of whole-genome CNAs in 86 newly diagnosed childhood T-ALL cases using a high-density single-nucleotide polymorphism array. We analyzed the presence of whole-genome CNAs with respect to immunophenotype, clinical features, and treatment outcomes. A total of 769 CNAs, including trisomies, duplications, deletions, and segmental loss of heterozygosity, were detected in 86 analyzed samples. Gain or loss of chromosomal regions exceeding 10 Mb occurred in 46 cases (53%), including six cases (7%) with complex chromosomal alterations. We observed that microdeletions in selected genes (e.g., FIP1L1 and PDGFRB) were related to the clinical features. Interestingly, 13% of samples have a duplication of the two loci (MYB and AIH1—6q23.3), which never occurred alone. Single-nucleotide polymorphism array significantly improved the molecular characterization of pediatric T-ALL. Further studies with larger cohorts of patients may contribute to the selection of prognostic CNAs in this group of patients.

Highlights

T-cell acute lymphoblastic leukemia (T-ALL) accounts for ∼15% of pediatric ALL cases [1]
The study was based on an analysis of scanned data files that were generated with the Chromosome Analysis Suite v 3.3 (ChAS; Thermo Fisher Scientific)
Our analysis shows that the profile of copy number abnormalities (CNAs) is associated with the immunophenotypic and clinical features of T-ALL

Summary

Introduction

T-cell acute lymphoblastic leukemia (T-ALL) accounts for ∼15% of pediatric ALL cases [1]. T-cell acute lymphoblastic leukemia is a biologically heterogeneous malignancy with numerous genetic aberrations in the leukemic genome. T-cell acute lymphoblastic leukemia has been divided into four subtypes according to the European Group for the Immunological Classification of Leukemia. The prognostic factors and risk stratification are different in T-ALL when compared to B-lineage leukemia. Minimal residual disease (MRD) response plays an essential role in the risk group assignment; leukocytosis and age at diagnosis are not independent prognostic factors in T-ALL [5]. Because most patients with relapse were originally stratified into an intermediate risk group, none of the existing prognostic genetic markers were efficient enough to predict treatment outcome in TALL. Associations of molecular lesions with specific T-ALL subtypes, clinical features, and outcomes have been documented [9]

Objectives

Methods

Results

Conclusion