Genomic profiling of adult acute lymphoblastic leukemia by single nucleotide polymorphism oligonucleotide microarray and comparison to pediatric acute lymphoblastic leukemia

Abstract

The online version of this article has a Supplementary Appendix. BackgroundDifferences in survival have been reported between pediatric and adult acute lymphoblastic leukemia. The inferior prognosis in adult acute lymphoblastic leukemia is not fully understood but could be attributed, in part, to differences in genomic alterations found in adult as compared to in pediatric acute lymphoblastic leukemia. Design and MethodsWe compared two different sets of high-density single nucleotide polymorphism array genotyping data from 75 new diagnostic adult and 399 previously published diagnostic pediatric acute lymphoblastic leukemia samples. The patients' samples were randomly acquired from among Caucasian and Asian populations and hybridized to either Affymetrix 50K or 250K single nucleotide polymorphism arrays. The array data were investigated with Copy Number Analysis for GeneChips (CNAG) software for allele-specific copy number analysis. ResultsThe high density single nucleotide polymorphism array analysis of 75 samples of adult acute lymphoblastic leukemia led to the identification of numerous cryptic and submicroscopic genomic lesions with a mean of 7.6 genomic alterations per sample. The patterns and frequencies of lesions detected in the adult samples largely reproduced known genomic hallmarks detected in previous single nucleotide polymorphism-array studies of pediatric acute lymphoblastic leukemia, such as common deletions of 3p14.2 (FHIT), 5q33.3 (EBF), 6q, 9p21.3 (CDKN2A/B), 9p13.2 (PAX5), 13q14.2 (RB1) and 17q11.2 (NF1). Some differences between adult and pediatric acute lymphoblastic leukemia were identified when the pediatric data set was partitioned into hyperdiploid and non-hyperdiploid cases and then compared to the nearly exclusively non-hyperdiploid adult samples. In this analysis, adult samples had a higher rate of deletions of chromosome 17p (TP53) and duplication of 17q. ConclusionsOur analysis of adult acute lymphoblastic leukemia cases led to the identification of new potential target lesions relevant for the pathogenesis of acute lymphoblastic leukemia. However, no unequivocal pattern of submicroscopic genomic alterations was found to separate adult acute lymphoblastic leukemia from pediatric acute lymphoblastic leukemia. Therefore, apart from different therapy regimen, differences of prognosis between adult and pediatric acute lymphoblastic leukemia are probably based on genetic subgroups according to cytogenetically detectable lesions but not focal genomic copy number microlesions.Key words: SNP-array; adult ALL; pediatric ALL; comparative study.Citation: Okamoto R, Ogawa S, Nowak D, Kawamata N, Akagi T, Kato M, Sanada M, Weiss T, Haferlach C, Dugas M, Ruckert C, Haferlach T, and

Precursor B-acute lymphoblastic leukemia occurring in patients with a history of prior malignancies: is it therapy-related?

“…19 A recent study using single nucleotide polymorphism oligonucleotide microarray found microdeletion of 17p (TP53) in 11% of all adult precursor B-ALL. 20 We found that hypodiploidy, particularly with complete loss of chromosome 5, 7 and 17(17p), was significantly more frequent among group 1 patients and all patients with this anomaly had received alkylating agents. This finding parallels the common cytogenetic alterations reported in t-MN after alkylating chemotherapy.…”

Genomic profiling of high-risk acute lymphoblastic leukemia

“…Similarly, there remains a substantial proportion of ALL cases that lack known cytogenetic alterations and fail therapy, and the frequency of these cases rises with increasing age. Compared with childhood leukemia, there is a lack of detailed, high-resolution genomic profiling data from adolescent and adult ALL, [95][96][97] which has a markedly inferior outcome to that of childhood ALL. The frequency of Ph þ ALL rises progressively with increasing age, but this alone does not account for the poor outcome of ALL with increasing age, and at present it is unclear whether the frequency of poorrisk mutations and expression profiles observed in pediatric ALL will be recapitulated in the adult setting.…”

Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia

“…4,7,8 Whether the pattern of microdeletions, as ascertained by single nucleotide polymorphism (SNP) array analysis, also differs between childhood and adult BCP ALL is less well clarified because most analyses of ALL have been performed on pediatric cases. 9,10 In fact, SNP array findings in adult ALL have so far been reported in only three larger series, [11][12][13] one of which focused solely on IKZF1 deletions. 13 The two other studies 11,12 identified similar gene deletions to those found in pediatric cases, namely losses of CDKN2A, PAX5, IKZF1, ETV6, RB1, EBF1 and LEF1.…”

“…9,10 In fact, SNP array findings in adult ALL have so far been reported in only three larger series, [11][12][13] one of which focused solely on IKZF1 deletions. 13 The two other studies 11,12 identified similar gene deletions to those found in pediatric cases, namely losses of CDKN2A, PAX5, IKZF1, ETV6, RB1, EBF1 and LEF1. However, these results were based on quite small cohorts of patients, comprising 45 and 75 adult ALL patients, respectively.…”