Identification of a Single-Nucleotide Polymorphism within CDH2 Gene Associated with Bone Morbidity in Childhood Acute Lymphoblastic Leukemia survivors

Abstract

Aim: To identify genetic markers associated with late treatment-related skeletal morbidity in survivors of childhood acute lymphoblastic leukemia (ALL). Patients & methods: To this end, we measured the association between reduction in bone mineral density or vertebral fractures prevalence and variants from 1039 genes derived through whole exome sequencing in 242 childhood ALL survivors. Top-ranking variants were confirmed through genotyping, and further explored with stratified analyses and multivariable models. Results: The minor allele of rs1944294 in CDH2 gene was associated with bone geometrical parameter, trabecular cross-sectional area (p = 0.001). The association was modulated by radiation therapy (p = 0.001) and post-treatment time (p = 0.0002). Conclusion: The variant in CDH2 gene is a potential novel risk factor of bone morbidity in survivors of childhood ALL.

Bone mineral density surveillance for childhood, adolescent, and young adult cancer survivors: evidence-based recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group

“…CAYA cancer survivors are at increased risk of low BMD (moderate-quality evidence), 6,7,[9][10][11] very low BMD (moderate-quality evidence), 6,7,9,10,[30][31][32][33][34][35][36][37][39][40][41][42][43][44][47][48][49][50][51][52][53][54][55][58][59][60][61][62]64,[66][67][68][69][70][71] and lower BMD Z-scores (moderatequality evidence) after a follow-up period ranging from 2•7 to 27•2 years. 30,31,33,38,39,41,43,<...…”

“…density surveillance? Risk and risk factors for low BMD, very low BMD, lower BMD Z-score, and fractures in CAYA cancer survivors diagnosed up to 25 years of age Very low BMD (Z-score ≤10,[30][31][32][33][34][35][36][37][39][40][41][42][43][44][47][48][49][50][51][52][53][54][55][58][59][60][61][62]64,[66][67][68][69][70][71] …”

miR-495-3p Sensitizes BCR::ABL1 Expressing Leukemic cells to Tyrosine Kinase Inhibitors by Targeting Multidrug Resistance 1 Gene including in T315I Mutated cells

“…Indeed, the up-regulation of these target genes allowed to stratify hematopoietic cells from BC and CP (Figure 5D). Among these target genes, several have already been described as upregulated during BC such as TM4SF1, ZNF827, KLHL5 , and CTNND2 [32,41], or implicated in leukemia pathophysiology such as GAB1, LHX2, THRB , and CDH2 [42–45] (Figure 5D). Next, we built a protein-protein interaction network using this gene set.…”

An Epitope Platform for Safe and Effective HTLV-1-Immunization: Potential Applications for mRNA and Peptide-Based Vaccines

“…When altered, these two proteins relate to tumorigenesis [ 26 ]. Cadherin-2 (APQVLP) may be associated with reduction in bone mineral density or vertebral fracture prevalence in survivors of childhood acute lymphoblastic leukemia [ 27 ]. Constitutive coactivator of PPAR-gamma-like protein 2 (QLPPTA) deletion is associated with autism [ 28 ].…”

“…Cadherin-2 (APQVLP) may be associated with reduction in bone mineral density or vertebral fracture prevalence in survivors of childhood acute lymphoblastic leukemia [ 27 ].…”