title: Linking genomic lesions with minimal residual disease improves prognostic stratification in children with T-cell acute lymphoblastic leukaemia.
abstract: Multiple lesions in genes that are involved in cell cycle control, proliferation, survival and differentiation underlie T-cell acute lymphoblastic leukaemia (T-ALL). We translated these biological insights into clinical practice to improve diagnostic work-ups and patient management. Combined interphase fluorescence in situ hybridization (CI-FISH), single nucleotide polymorphism (SNP), and gene expression profiles (GEP) were applied in 51 children with T-ALL who were stratified according to minimal residual disease (MRD) risk categories (AIEOP-BFM ALL2000). CI-FISH identified type A abnormalities in 90% of patients. Distribution of each was in line with the estimated incidence in childhood T-ALL: 37.5% TAL/LMO, 22.5% HOXA, 20% TLX3, 7.5% TLX1, and 2.5% NKX2-1. GEP predictions concurred. SNP detected type B abnormalities in all cases, thus linking type A and B lesions. This approach provided an accurate, comprehensive genomic diagnosis and a complementary GEP-based classification of T-ALL in children. Dissecting primary and secondary lesions within MRD categories could improve prognostic criteria for the majority of patients and be a step towards personalized diagnosis.
authors.affiliation: Hematology Unit, University of Perugia, Polo Unico S.M. Misericordia, Perugia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: La Starza
authors.forename: Antonella
authors.initials: A
authors.lastname: Lettieri
authors.forename: Valentina
authors.initials: V
authors.lastname: Pierini
authors.forename: Valeria
authors.initials: V
authors.lastname: Nofrini
authors.forename: Paolo
authors.initials: P
authors.lastname: Gorello
authors.forename: Simona
authors.initials: S
authors.lastname: Songia
authors.forename: Barbara
authors.initials: B
authors.lastname: Crescenzi
authors.forename: Geertruy
authors.initials: G
authors.lastname: Te Kronnie
authors.forename: Marco
authors.initials: M
authors.lastname: Giordan
authors.forename: Anna
authors.initials: A
authors.lastname: Leszl
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Franco
authors.initials: F
authors.lastname: Aversa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Valentino
authors.initials: V
authors.lastname: Conter
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cazzaniga
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D020022:Genetic Predisposition to Disease / Q000235:genetics; D023281:Genomics / Q000379:methods*; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D059785:Karyotype; D008297:Male; D018365:Neoplasm, Residual / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics*; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity