Myeloperoxidase (MPO) is a heme containing enzyme involved in the oxygen-dependent microbicidal activity of human polymorphonuclear leukocytes (PMN). Complete hereditary and acquired MPO deficiencies are defined as lack of peroxidase activity in PMN. Using this criterion, we studied a patient with complete hereditary MPO deficiency, and a MPO deficient variant cell line of HL-60 (HL-60-A7), which we used as a model for acquired MPO deficiency. Western blot analysis showed complete absence of mature and precursor protein of MPO both in PMN from the patient and in HL-60-A7 cells. PMN from both parents had one half of normal levels of these proteins. To study further the molecular basis of this defect, we isolated an intron specific probe for MPO and used it and a cDNA probe. Both normal human bone marrow cells and the promyelocytic HL-60 leukemia cells contained MPO mRNA species of 2.8, 3.3, approximately 4, and greater than 8 kilobase (kb). The transcripts of greater than 8 and approximately 4 kb contained sequences hybridizing to a probe specific for intron 7 of the MPO gene. Bone marrow cells of the MPO deficient patient contained two species of heterogeneous nuclear (hn) RNA of greater than 8 and approximately 4 kb, but only trace amounts of the normal sized 3.3 kb MPO mRNA and undetectable 2.8 kb MPO mRNA. HL-60-A7 cells contained both greater than 8 and approximately 4 kb hnRNA, but only small amounts of normal sized 2.8 kb MPO mRNA and undetectable levels of the 3.3 kb mRNA. Southern blot analyses revealed no gross alteration of the MPO gene in both cases. Our results suggest that a pretranslational defect is one mechanism leading to MPO deficiency.

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