TY - JOUR
T1 - Hidden abnormalities and novel classification of t(15;17) acute promyelocytic leukemia (APL) based on genomic alterations
AU - Akagi, Tadayuki
AU - Shih, Lee Yung
AU - Kato, Motohiro
AU - Kawamata, Norihiko
AU - Yamamoto, Go
AU - Sanada, Masashi
AU - Okamoto, Ryoko
AU - Miller, Carl W.
AU - Liang, Der Cherng
AU - Ogawa, Seishi
AU - Koeffler, H. Phillip
PY - 2009/2/19
Y1 - 2009/2/19
N2 - Acute promyelocytic leukemia (APL) is a hematopoietic malignant disease characterized by the chromosomal transloca-tion t(15;17), resulting in the formation of the PML-RARA gene. Here, 47 t(15;17) APL samples were analyzed with high-density single-nucleotide polymorphism microarray (50-K and 250-K SNP-chips) using the new algorithm AsCNAR (allele-specific copy-number analysis using anonymous references). Copy-number-neutral loss of heterozygosity (CNN-LOH) was identified at chromosomes 10q (3 cases), 11p (3 cases), and 19q (1 case). Twenty-eight samples (60%) did not have an obvious alteration (normal-copy-number [NC] group). Nineteen samples (40%) showed either one or more genomic abnormalities: 8 samples (17%) had trisomy 8 either with or without an additional duplication, deletion, or CNN-LOH (+8 group); and 11 samples (23%) had genomic abnormalities without trisomy 8 (other abnormalities group). These chromosomal abnormalities were acquired somatic mutations. Interestingly, FLT3-ITD mutations (11/47 cases) occurred only in the group with no genomic alteration (NC group). Taken together, these results suggest that the pathway of development of APL differs in each group: FLT3-ITD, tri-somy 8, and other genomic changes. Here, we showed for the first time hidden abnormalities and novel disease-related genomic changes in t(15;17) APL.
AB - Acute promyelocytic leukemia (APL) is a hematopoietic malignant disease characterized by the chromosomal transloca-tion t(15;17), resulting in the formation of the PML-RARA gene. Here, 47 t(15;17) APL samples were analyzed with high-density single-nucleotide polymorphism microarray (50-K and 250-K SNP-chips) using the new algorithm AsCNAR (allele-specific copy-number analysis using anonymous references). Copy-number-neutral loss of heterozygosity (CNN-LOH) was identified at chromosomes 10q (3 cases), 11p (3 cases), and 19q (1 case). Twenty-eight samples (60%) did not have an obvious alteration (normal-copy-number [NC] group). Nineteen samples (40%) showed either one or more genomic abnormalities: 8 samples (17%) had trisomy 8 either with or without an additional duplication, deletion, or CNN-LOH (+8 group); and 11 samples (23%) had genomic abnormalities without trisomy 8 (other abnormalities group). These chromosomal abnormalities were acquired somatic mutations. Interestingly, FLT3-ITD mutations (11/47 cases) occurred only in the group with no genomic alteration (NC group). Taken together, these results suggest that the pathway of development of APL differs in each group: FLT3-ITD, tri-somy 8, and other genomic changes. Here, we showed for the first time hidden abnormalities and novel disease-related genomic changes in t(15;17) APL.
UR - http://www.scopus.com/inward/record.url?scp=61849146788&partnerID=8YFLogxK
U2 - 10.1182/blood-2007-12-130260
DO - 10.1182/blood-2007-12-130260
M3 - 文章
C2 - 19109227
AN - SCOPUS:61849146788
SN - 0006-4971
VL - 113
SP - 1741
EP - 1748
JO - Blood
JF - Blood
IS - 8
ER -