PAX5 deletion is common and concurrently occurs with CDKN2A deletion in B-lineage acute lymphoblastic leukemia

Kim, Miyoung; Choi, Jung Eun; She, Cha Ja; Hwang, Sang Mee; Shin, Hee Young; Ahn, Hyo Seop; Yoon, Sung-Soo; Kim, Byoung Kook; Park, Myoung Hee; Lee, Dong Hoon

doi:10.1016/j.bcmd.2011.04.003

Cited by 28 publications

(31 citation statements)

References 16 publications

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“…Homozygous deletions have been shown to be associated with poor outcome, whereas heterozygous deletions tend to represent favorable outcomes. 16,31 Moreover, this study also found co-deletion of CDKN2A/2B and IKZF1 in majority of the cases (5 in 9, 55.6%). It has been noticed that co-deletion of both genes was a marker of shorter survival in adult B-ALL patients.…”

Section: Discussionsupporting

confidence: 70%

“…However, the high occurrence of homozygous deletions (55.6%) revealed in this study has not been reported by others. Homozygous deletions have been shown to be associated with poor outcome, whereas heterozygous deletions tend to represent favorable outcomes . Moreover, this study also found co‐deletion of CDKN2A/2B and IKZF1 in majority of the cases (5 in 9, 55.6%).…”

Section: Discussionsupporting

confidence: 63%

“…Secondly, CMA results are valuable in the diagnosis and cytogenetic risk assessment in oncologic specimens, based on our and all other collective evidence. Thirdly, considering its high resolution, CMA can be particularly useful as a replacement for FISH panel tests for the evaluation of other bone marrow disorders with multiple genomic gains and losses, for example, FISH panels aiming at CNAs in CLL, myelodysplastic syndrome (MDS), and multiple myeloma (MM), as long as there are sufficient numbers of neoplastic cells or they are enriched in some way; for detection of cryptic CNAs that are beyond the resolution of FISH test; for risk assessment by the detection of deletions involving the IKZF1 , ETV6 , PAX5 , and RB1 genes in ALL patients; and in cases with suspected gene amplification of unknown origin. Lastly, with the advantage of obviating the need for cell culture, CMA is useful in samples with a normal karyotype or culture failure.…”

Section: Discussionmentioning

confidence: 99%

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Chromosomal microarray analysis is superior in identifying cryptic aberrations in patients with acute lymphoblastic leukemia at diagnosis/relapse as a single assay

Chen

Heng

Lim

et al. 2019

Int J Lab Hematology

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Introduction Conventional cytogenetics (CC) is important in diagnosis, therapy, monitoring of post‐transplant bone marrow, and prognosis assessment of acute lymphoblastic leukemia (ALL). However, due to the nature of ALL, CC often encounters difficulties of complex karyotype, poor chromosome morphology, low mitotic index, or normal cells dividing only. In contrast, chromosomal microarray analysis (CMA) showed a specificity >99% and a sensitivity of 100% in chronic lymphocytic leukemia (CLL) patients. Here, we report our experience with CMA on adult ALL patients. Methods Thirty‐three bone marrow/blood samples from ALL patients (aged 18‐79 years, median 44) at diagnosis/relapse, analyzed by CC and/or fluorescence in situ hybridization (FISH), were recruited. Chromosomal microarray analysis results were compared with CC. Fluorescence in situ hybridization analysis, if available, was applied when there was a discrepancy. Results Copy‐neutral loss‐of‐heterozygosity (CN‐LOH) was found in 8 cases (24.2%). Only CN‐LOH at 9p was recurrent (3 cases, 9.1%). Copy number alterations (CNAs) were detected in 6 of 9 cases (66.7%) with normal karyotypes, in 3 of 5 cases (60.0%) with sole “balanced” translocations, and in 18 of 19 cases (94.7%) with complex karyotypes. Common CNAs involved CDKN2A/2B (30.3%), IKZF1 (27.3%), PAX5 (9.1%), RB1 (9.1%), BTG1 (6.7%), and ETV6 (6.7%), which regulate cell cycle, B lymphopoiesis, or act as tumor suppressors in ALL. Copy number alteration detection rate by CMA was 81.8% (27 of 33 cases) as compared to 57.6% (19 of 33 cases) by CC. Conclusion Incorporation of CMA as a routine clinical test at the time of diagnosis/relapse, in conjunction with CC and/or FISH, is highly recommended.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

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Chromosomal microarray analysis is superior in identifying cryptic aberrations in patients with acute lymphoblastic leukemia at diagnosis/relapse as a single assay

Chen

Heng

Lim

et al. 2019

Int J Lab Hematology

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“…CDKN2A reportedly influences the risk of developing ALL (31). PAX5 is also reportedly concurrently deleted in CDKN2A deletion in B-lineage ALL (32). Segmental LOH 9p could explain this concurrent deletion.…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Previously Cryptic Copy Number Alterations and Loss of Heterozygosity in Pediatric Acute Myeloid Leukemia and Myelodysplastic Syndrome Determined Using Combined Array Comparative Genomic Hybridization plus Single-Nucleotide Polymorphism Microarray Analyses

et al. 2014

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The combined array comparative genomic hybridization plus single-nucleotide polymorphism microarray (CGH+SNP microarray) platform can simultaneously detect copy number alterations (CNA) and copy-neutral loss of heterozygosity (LOH). Eighteen children with acute myeloid leukemia (AML) (n=15) or myelodysplastic syndrome (MDS) (n=3) were studied using CGH+SNP microarray to evaluate the clinical significance of submicroscopic chromosomal aberrations. CGH+SNP microarray revealed CNAs at 14 regions in 9 patients, while metaphase cytogenetic (MC) analysis detected CNAs in 11 regions in 8 patients. Using CGH+SNP microarray, LOHs>10 Mb involving terminal regions or the whole chromosome were detected in 3 of 18 patients (17%). CGH+SNP microarray revealed cryptic LOHs with or without CNAs in 3 of 5 patients with normal karyotypes. CGH+SNP microarray detected additional cryptic CNAs (n=2) and LOHs (n=5) in 6 of 13 patients with abnormal MC. In total, 9 patients demonstrated additional aberrations, including CNAs (n=3) and/or LOHs (n=8). Three of 15 patients with AML and terminal LOH>10 Mb demonstrated a significantly inferior relapse-free survival rate (P=0.041). This study demonstrates that CGH+SNP microarray can simultaneously detect previously cryptic CNAs and LOH, which may demonstrate prognostic implications.Graphical Abstract

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“…PAX5 deletion was frequently accompanied by deletion in CDKN2A/2B on 9p21.3 adjacent to PAX5 (9p13.2), IKZF1 (7p12.2), and ETV6 (12p13.2). Concurrent deletion of PAX5 and CDKN2A/2B suggests that they are common targets in the pathogenesis of BCP-ALL (9,32). The concurrent presence of IKZF1 deletions and at least one additional deletion in the PAX5, CDKN2A/ 2B, or PAR1 region in the absence of ERG deletions has been reported.…”

Section: Discussionmentioning

confidence: 92%

Frequency of copy number abnormalities in common genes associated with B-cell precursor acute lymphoblastic leukemia cytogenetic subtypes in Brazilian children

Barbosa¹,

Terra-Granado²,

Magalhães³

et al. 2015

Cancer Genetics

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PAX5 deletion is common and concurrently occurs with CDKN2A deletion in B-lineage acute lymphoblastic leukemia

Cited by 28 publications

References 16 publications

Chromosomal microarray analysis is superior in identifying cryptic aberrations in patients with acute lymphoblastic leukemia at diagnosis/relapse as a single assay

Chromosomal microarray analysis is superior in identifying cryptic aberrations in patients with acute lymphoblastic leukemia at diagnosis/relapse as a single assay

Clinical Significance of Previously Cryptic Copy Number Alterations and Loss of Heterozygosity in Pediatric Acute Myeloid Leukemia and Myelodysplastic Syndrome Determined Using Combined Array Comparative Genomic Hybridization plus Single-Nucleotide Polymorphism Microarray Analyses

Frequency of copy number abnormalities in common genes associated with B-cell precursor acute lymphoblastic leukemia cytogenetic subtypes in Brazilian children

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