Abstract
Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), but additional chromosomal abnormalities (ACA) and other rearrangements can contribute in the development of the whole leukemic phenotype. We hypothesized that some ACA not detected by conventional techniques may be informative of the onset of APL. We performed the high-resolution SNP array (SNP-A) 6.0 (Affymetrix) in 48 patients diagnosed with APL on matched diagnosis and remission sample. Forty-six abnormalities were found as an acquired event in 23 patients (48%): 22 duplications, 23 deletions and 1 Copy-Neutral Loss of Heterozygocity (CN-LOH), being a duplication of 8(q24) (23%) and a deletion of 7(q33-qter) (6%) the most frequent copy-number abnormalities (CNA). Four patients (8%) showed CNAs adjacent to the breakpoints of the translocation. We compared our results with other APL series and found that, except for dup(8q24) and del(7q33-qter), ACA were infrequent (≤3%) but most of them recurrent (70%). Interestingly, having CNA or FLT3 mutation were mutually exclusive events. Neither the number of CNA, nor any specific CNA was associated significantly with prognosis. This study has delineated recurrent abnormalities in addition to t(15;17) that may act as secondary events and could explain leukemogenesis in up to 40% of APL cases with no ACA by conventional cytogenetics.
Highlights
Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21) and the corresponding fusion gene PML-RARA.Additional chromosomal abnormalities (ACA) have been traditionally analyzed by conventional cytogenetics and fluorescence in situ hybridization (FISH)
The single-nucleotide polymorphism array (SNP-A) has become a powerful tool to perform what has been called ‘‘molecular karyotyping’’, because it increases the resolution of conventional cytogenetics and detects a wider spectrum of abnormalities than FISH and other targeted techniques
This study shows that high-resolution SNP-A analysis reveals
Summary
Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21) and the corresponding fusion gene PML-RARA. Additional chromosomal abnormalities (ACA) have been traditionally analyzed by conventional cytogenetics and fluorescence in situ hybridization (FISH). The single-nucleotide polymorphism array (SNP-A) has become a powerful tool to perform what has been called ‘‘molecular karyotyping’’, because it increases the resolution of conventional cytogenetics and detects a wider spectrum of abnormalities than FISH and other targeted techniques. SNP-A are able to uncover regions of copyneutral loss of heterozygosity (CN-LOH), a known phenomenon that occurs in cancer and which is not detectable by conventional cytogenetics.[1]. Most reports studying ACA in APL with SNP-A have used low resolution arrays or have not systematically matched tumor and germline sample,[2,3] which is the only certain way to rule out copy-number variations (CNV).[4] Our interest in the clinical
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