Microarray based on comparative genomic hybridization reveals new recurrent genetic aberrations in acute myeloid leukemia
Authors: J. Prada-Arismendy, J.J. Lopez-Rivera, Y. Carrillo, E. Castillo, W. Castellanos
Journal: Annals of Oncology (2018)

Background: Nearly half of acute myeloid leukemia (AML) patients show a normal karyotype, being the most heterogeneous group of patients. Because cytogenetic alterations are important prognostic factors, cryptic copy number alterations could explain some of the heterogeneity. Microarray-based comparative genomic hybridization (aCGH) has recently been used to study hematologic malignancies and has shown increased diagnostic yield, especially for cryptic findings. Methods: Paired blood samples were collected from 12 AML patients before and after treatment induction during 2015-2017. Written informed consent was obtained at Hospital Manuel Uribe Angel (Envigado-Colombia) and Clínica Somer (Rionegro-Antioquia). The clinical records were reviewed to obtain important clinical variables. After DNA isolation, we used the CytoScan® 750K Array that enables the detection high resolution copy number across the genome as well as providing allelic imbalance information from single nucleotide polymorphisms (SNPs). This high density array contains greater than 750,000 markers for copy number and approximately 200,000 genotype-able SNPs which provide high resolution copy number, accurate breakpoint estimation, and loss of heterozygosity (LOH) detection. Results: A total of 53 copy number variations (CNV) were found. Most of the CNVs found in the patients before receiving the induction treatment (85%) remained after completing the induction phase. Only 15% of the alterations found disapeared after treatment. More than half of the alterations found are LOH (58%), followed by deletions (32%), and additions (8%). Chr X was the most affected (15%), most of which were LOH. The alterations found are described in detail in the table.Table: 38PCasesSexKaryotypeLeukemia subtypeBlasts(%)OutcomeCNV found before treatmentCNV found after treatment5FNo dataM385CRAdd (3q23)RemainsDel (9p21.1-p22.1)DisapearLOH 11p11.2DisapearLOH 19q13.42DisapearLOH todo elcromosoma XDisapear10FNo dataM1M274CRDel 13q12.2DisapearRemainsLOH X p11.22Appears LOH7q11.2211F46,XX (6) and hypodiploid (4)M438RDel 3 p21.31RemainsDel 5q23.3RemainsDel 7q11.22q36.1RemainsDel 10q11.21q23RemainsDel 11q13.4RemainsDel 12p13.2RemainsDel 12q12q24RemainsDel 16q24.1RemainsDel 17p13.1RemainsDel 17q11.2q12RemainsLOH Xp11.23RemainsLOH Xq11.1q13.1Remains12F46,XX (5), t(8;21 q22q22) (15)M220CRLOH Xq11.1q26Remains13MNormalNot classified68RLOH 1q21.3DisapearDel 10q11.22Remains15M46,XY,add(3p?), -5(10), +15(2), +M(2)CP 10.M1M247PRLOH 3p25.1RemainsAdd 6q21RemainsMon 7Remains17M45, X(-Y), t(8;21)(q22;q22)(9)M066CRLOH 2p22RemainsLOH 12q13RemainsAdd 16p12Remains18FNormalNot classified26CRLOH 3p21RemainsDel 15q11RemainsLOH Xq22Remains19FNo dataM0M165CRLOH 1q42RemainsDel 13q14RemainsLOH 21q21DisapearLOH Xq11q21RemainsS3MNormalM491RLOH 1q22RemainsLOH 3q26RemainsLOH 4qRemainsLOH 5q31RemainsLOH 6p25RemainsLOH 6q25RemainsLOH 7q34RemainsLOH 10p15RemainsLOH 11q14RemainsLOH 14q23RemainsLOH 15q14RemainsLOH 18p11RemainsLOH 18q12RemainsLOH 22q13RemainsAppears Del 7p14S4M46,XY,t(15;17)M396CRDel 7p21RemainsDel 9p24RemainsLOH 10q23RemainsAdd17q21Disapear6MNo dataM360DiedNormal14F46,XX,t(15;17)M3No dataDiedDel 7q11.21LOH 19p13.3LOH Xp11.3LOH Xq11.1q27.2Add Xq26.3 Open table in a new tab Conclusions: Induction treatment does not cause recovery of cytogenetic alterations in most cases. The perspective is to expand the cohort and make a correlation between the molecular findings and the outcomes of the patients, to define new markers related to prognosis and response to treatment. Legal entity responsible for the study: Instituto Tecnológico Metropolitano. Funding: Colciencias (Grant 669-2014). Disclosure: All authors have declared no conflicts of interest.