title: SNP array analysis of acute promyelocytic leukemia may be of prognostic relevance and identifies a potential high risk group with recurrent deletions on chromosomal subband 1q31.3.
abstract: To search for new copy number alterations (CNAs) in acute promyelocytic leukemia (APL), we analyzed DNA from leukemic blasts of 93 acute promyelocytic leukemia (APL) patients with Genome-Wide SNP 6.0 arrays (SNP-A). We identified 259 CNAs consisting of 170 heterozygous deletions, 82 amplifications, and 7 regions of copy number neutral loss of heterozygosity. One of the most common CNAs was a deletion on chromosomal subband 1q31.3 in 13 of 93 (14%) patients encompassing the coding regions for the microRNAs mir181a1/b1. In multivariable analysis with the covariates age, white blood cell count, platelet count, and FLT3-ITD/FLT3 D835 mutations we found that after adjustment for patients' age (P<0.0001), patients with 2 or more CNAs detected by SNP-A had a higher risk of death (hazard ratio=5.942, P=0.0015) than patients with 0 or 1 CNA. Deletions of 1q31.3 were associated with a higher number of CNAs (median 2 vs. 8, P<0.0001) and were a strong independent prognostic factor for an increased risk of relapse (hazard ratio=28.9, P=0.0031). This study presents a comprehensive assessment of new CNAs as pathomechanistically relevant targets and possible prognostic factors which could refine risk stratification of APL.
authors.affiliation: Department of Hematology and Oncology, Medical Faculty Mannheim, University of Heidelberg, Germany. daniel.nowak@medma.uni-heidelberg.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Nowak
authors.forename: Marion
authors.initials: M
authors.lastname: Klaumuenzer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hanfstein
authors.forename: Maximilian
authors.initials: M
authors.lastname: Mossner
authors.forename: Florian
authors.initials: F
authors.lastname: Nolte
authors.forename: Verena
authors.initials: V
authors.lastname: Nowak
authors.forename: Julia
authors.initials: J
authors.lastname: Oblaender
authors.forename: Anna
authors.initials: A
authors.lastname: Hecht
authors.forename: Gero
authors.initials: G
authors.lastname: Hütter
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Alexander
authors.initials: A
authors.lastname: Kohlmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Jan
authors.initials: J
authors.lastname: Braess
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Seifarth
authors.forename: Alice
authors.initials: A
authors.lastname: Fabarius
authors.forename: Philipp
authors.initials: P
authors.lastname: Erben
authors.forename: Susanne
authors.initials: S
authors.lastname: Saussele
authors.forename: Martin C
authors.initials: MC
authors.lastname: Müller
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
authors.forename: Thomas
authors.initials: T
authors.lastname: Buechner
authors.forename: Christel
authors.initials: C
authors.lastname: Weiss
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.forename: Eva
authors.initials: E
authors.lastname: Lengfelder
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002648:Child; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D056915:DNA Copy Number Variations; D005260:Female; D017353:Gene Deletion; D006801:Humans; D053208:Kaplan-Meier Estimate; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012307:Risk Factors; D018709:Statistics, Nonparametric; D014178:Translocation, Genetic
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein