Mercaptopurine intolerance is an adverse effect of mercaptopurine administration in pediatric acute lymphoblastic leukemia. Recently,
NUDT15
variants were identified as a major determinant of mercaptopurine intolerance. Two
NUDT15
variants, c.36_37insGGAGTC and c.415C > T, are located on exons 1 and 3, respectively. Patients with heterozygous c.36_37insGGAGTC and c.415C > T can be either compound heterozygous with two variants on different alleles or heterozygous with both variants on the same allele. Because patients with biallelic
NUDT15
variants are extremely sensitive to mercaptopurine, clinical identification of
NUDT15
diplotype would be advantageous. A cohort of 37 patients with c.36_37insGGAGTC and c.415C > T
NUDT15
variants were selected for haplotyping by targeted sequencing.
NUDT15
complementary DNA was amplified and sequenced by 300-bp paired-end sequencing on Illumina MiSeq. Of the 37 patients carrying
NUDT15
variants, 35 had heterozygous
NUDT15
*1/*2 variants and two had compound heterozygous
NUDT1
5*3/*6 and
NUDT15
*2/*7 variants. These two patients with compound heterozygous variants could only tolerate low doses of mercaptopurine, similar to patients with homozygous
NUDT15
variants. Targeted sequencing of
NUDT15
cDNA can be used to determine
NUDT15
diplotype and identify patients with compound heterozygous
NUDT15
variants
.
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