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H. Mizumaki et al.
other 33 patients with Exon1mut, HLA-A or HLA-B alleles that acquired Exon1mut could not be determined or deduced due to very low VAF (<0.2%), the absence of allele-specif- ic SNP near Exon1mut in HLA-A or HLA-B alleles that are useful for identify missing HLA alleles, or the absence of coexisting 6pLOH. For the 68 patients in whom HLA alle- les that acquired Exon1mut could be determined, the follow- ing 12 alleles were identified: A*02:01 (n=2), A*02:06 (n=15), A*02:07 (n=1), A*31:01 (n=3), B*13:01 (n=2), B*40:01 (n=3), B*40:02 (n=31), B*40:03 (n=1), B*44:03 (n=1), B*54:01 (n=6), B*55:02 (n=2), and B*56:01 (n=1)
A
(Figure 5A). HLA class I supertypes of these alleles, which are defined by similarities in the antigen-presenting amino-acid motif of HLA alleles, were confined to only four supertypes: A02, A03, B07, and B44, except for HLA- B*13:01 that does not belong to any of the 14 supertypes.21
When comparing the frequency of these 12 alleles between a healthy control population and our study cohort, 81% of 18,604 healthy Japanese individuals pos- sessed at least one of the 12 alleles, while the prevalence was 92% in the 353 patients with AA (P<0.001) and 100% in the 83 patients with 6pLOH (P<0.001) (Figure 5B), sug-
B
Figure 4. Temporal changes in allelic frequency of Exon1mut. (A) Allelic frequencies of Exon1mut determined at different time points in 13 patients and their disease status. (B) Representative scattergrams from UPN 213 showing a gradual decline in Exon1mut frequency over the course of 3 years. UPN: unique patient number; ddPCR: droplet digital polymerase chain reaction; CsA: cyclosporine A; VAF: variant allele frequency.
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haematologica | 2021; 106(6)