Molecular mechanism of MPO deficiency in blast cells. (A) Sanger sequencing of the intron 11 of MPO, showing a c.2031-2A>C mutation of the intronic 3′ splice acceptor site, which is heterozygous in germline (left) and homozygous in APL (middle). The right panel is a schematic representation of the 2 MPO alleles. (B) Polymerase chain reaction analysis of the MPO mRNA, showing intron 11 retention in the APL diagnosis sample (Diag) and not in the sample collected at the time of molecular complete remission(CR). A control mRNA (CTRL) was used to identify the normal size of MPO mRNA. The right panel is a schematic representation of the wild-type (WT) and mutant MPO mRNA. (C) Schematic overview of the molecular oncogenesis explaining this MPO-negative APL case. The patient is an asymptomatic heterozygote carrier of an MPO-deficient allele (MUT, left), who developed APL after t(15;17)(PML-RARA) translocation (middle). Because t(15;17) is located on chromosome 17 with the MPO-deficient allele, the 17q UPD results in homozygous MPO-deficient blast cells (right).