Acute promyelocytic leukemia (APL) is a hematopoietic malignant disease characterized by the chromosomal translocation t(15;17), resulting in the fusion of PML-RARA genes. We examined whether genomic alterations could be found other than t(15;17) using a sensitive technique in order to subcategorized this disease on the basis of genomic status. Thirty-three t(15;17) APL samples were analyzed with high-density single-nucleotide polymorphism microarray (50K SNP-chip) using the new algorithm AsCNAR (allele-specific copy-number analysis using anonymous references). Our analysis revealed that 10q (2 cases), 11p (3 cases) and 19q (1 case) regions were identified as loss of heterozygosity with normal copy number [we call this somatic uniparental disomy (UPD)] that could not be detected by karyotypic analysis. Nineteen samples (58%, Group A) did not have an obvious alteration. Fourteen samples (42%) showed either one or more genomic abnormalities: 6/14 of these samples (18%, Group B) had trisomy 8 either with or without duplication, deletion, and UPD; and 8/14 of these samples (24%, Group C) had abnormalities without trisomy 8. Interestingly, FLT3-ITD mutation (7/33 cases) was found only in Group A. These results suggest that the pathway of development of APL differs in each group; FLT3-ITD, trisomy 8 (probably c-Myc gene), and unknown factor(s) are involved in group A, B, and C, respectively. Here, we showed for the first time hidden abnormalities and novel disease-related genomic regions in t(15;17) APL. Our technique may become a routine, rapid, robust technique for subclassification of APL and to screen for novel therapeutic targets.

Author notes

Disclosure: No relevant conflicts of interest to declare.