Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype.

Abstract:

BACKGROUND:Acute myeloid leukemia is a clonal hematopoietic malignant disease; about 45-50% of cases do not have detectable chromosomal abnormalities. Here, we identified hidden genomic alterations and novel disease-related regions in normal karyotype acute myeloid leukemia/myelodysplastic syndrome samples. DESIGN AND METHODS:Thirty-eight normal karyotype acute myeloid leukemia/myelodysplastic syndrome samples were analyzed with high-density single-nucleotide polymorphism microarray using a new algorithm: allele-specific copy-number analysis using anonymous references (AsCNAR). Expression of mRNA in these samples was determined by mRNA microarray analysis. RESULTS:Eighteen samples (49%) showed either one or more genomic abnormalities including duplication, deletion and copy-number neutral loss of heterozygosity. Importantly, 12 patients (32%) had copy-number neutral loss of heterozygosity, causing duplication of either mutant FLT3 (2 cases), JAK2 (1 case) or AML1/RUNX1 (1 case); and each had loss of the normal allele. Nine patients (24%) had small copy-number changes (< 10 Mb) including deletions of NF1, ETV6/TEL, CDKN2A and CDKN2B. Interestingly, mRNA microarray analysis showed a relationship between chromosomal changes and mRNA expression levels: loss or gain of chromosomes led, respectively, to either a decrease or increase of mRNA expression of genes in the region. CONCLUSIONS:This study suggests that at least one half of cases of normal karyotype acute myeloid leukemia/myelodysplastic syndrome have readily identifiable genomic abnormalities, as found by our analysis; the high frequency of copy-number neutral loss of heterozygosity is especially notable.

journal_name

Haematologica

journal_title

Haematologica

authors

Akagi T,Ogawa S,Dugas M,Kawamata N,Yamamoto G,Nannya Y,Sanada M,Miller CW,Yung A,Schnittger S,Haferlach T,Haferlach C,Koeffler HP

doi

10.3324/haematol.13024

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

213-23

issue

2

eissn

0390-6078

issn

1592-8721

pii

haematol.13024

journal_volume

94

pub_type

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