title: Feasibility of the AML profiler (Skyline™ Array) for patient risk stratification in a multicentre trial: a preliminary comparison with the conventional approach.
abstract: Deoxyribonucleic acid microarrays allow researchers to measure mRNA levels of thousands of genes in a single experiment and could be useful for diagnostic purposes in patients with acute myeloid leukaemia (AML). We assessed the feasibility of the AML profiler (Skyline™ Array) in genetic stratification of patients with de novo AML and compared the results with those obtained using the standard cytogenetic and molecular approach. Diagnostic bone marrow from 31 consecutive de novo AML cases was used to test MLL-PTD, FLT3-ITD and TKD, NPM1 and CEBPAdm mutations. Purified RNA was used to assess RUNX1-RUNX1T1, PML-RARα and CBFβ-MYH11 rearrangements. RNA remnants underwent gene expression profiling analysis using the AML profiler, which detects chromosomal aberrations: t(8;21), t(15;17), inv(16), mutations (CEBPAdm, ABD-NPM1) and BAALC and EVI1 expression. Thirty cases were successfully analysed with both methods. Five cases had FLT3-ITD. In one case, a t(8;21) was correctly detected by both methods. Four cases had inv(16); in one, the RNA quality was unsatisfactory and it was not hybridized, and in the other three, the AML profiler detected the genetic lesion - this being a rare type I translocation in one case. Two cases with acute promyelocytic leukaemia were diagnosed by both methods. Results for NPM1 mutations were concordant in all but two cases (2/11, non-ABD mutations). Analysis of costs and turnaround times showed that the AML profiler was no more expensive than the conventional molecular approach. These results suggest that the AML profiler could be useful in multicentre trials to rapidly identify patients with AML with a good prognosis. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Josep F
authors.initials: JF
authors.lastname: Nomdedéu
authors.affiliation: Servei d'Analisi de Microarrays, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Eulalia
authors.initials: E
authors.lastname: Puigdecanet
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Bussaglia
authors.affiliation: Laboratori de Referència de Catalunya, Barcelona, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Hernández
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Maite
authors.initials: M
authors.lastname: Carricondo
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Camino
authors.initials: C
authors.lastname: Estivill
authors.affiliation: Hematology Department, Hospital Universitari Mútua de Terrassa, Barcelona, Spain.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Martí-Tutusaus
authors.affiliation: Hematology Department, Hospital Clínico de Valencia, INCLIVA, Valencia, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Tormo
authors.affiliation: Hematology Department, Institut Recerca contra la Leucemia Josep Carreras (IJC), ICO Badalona Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Lurdes
authors.initials: L
authors.lastname: Zamora
authors.affiliation: Bioinformatic Platform, IIB Sant Pau, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Serrano
authors.affiliation: Laboraotory Service, UDIAT-CD, Parc Taulí Hospital Universitari, Sabadell, Spain.
authors.forename: Granada
authors.initials: G
authors.lastname: Perea
authors.affiliation: Hematology Department, Hospital Virgen de la Victoria, Màlaga, Spain.
authors.forename: Maria Paz Queipo
authors.initials: MPQ
authors.lastname: de Llano
authors.affiliation: Hematology Department, Hospital Arnau de Vilanova, Lleida, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: García
authors.affiliation: Hematology Department, Hospital de Bellvitge, L'Hospitalet de Llobregat, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sánchez-Ortega
authors.affiliation: Hematology Department, Institut Recerca contra la Leucemia Josep Carreras (IJC), ICO Badalona Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Ribera
authors.affiliation: Servei d'Analisi de Microarrays, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Nonell
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Aventin
authors.affiliation: Hematology Department, Institut Recerca contra la Leucemia Josep Carreras (IJC), ICO Badalona Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Solé
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Maria Salut
authors.initials: MS
authors.lastname: Brunet
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
mesh_terms: D005240:Feasibility Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D000090243:Nucleophosmin; D011379:Prognosis; D012306:Risk
keywords: acute myeloid leukaemia; gene expression profiling; leukaemia diagnostic; molecular genetics