AN ALLELIC ASSOCIATION IMPLICATES MYELOPEROXIDASE IN THE ETIOLOGY OF ACUTE PROMYELOCYTIC LEUKEMIA

Myeloperoxidase (MPO) catalyzes a reaction between chloride and hydrog en peroxide to generate hypochlorous acid and other reactive compounds that have been linked to DNA damage. The MPO gene is expressed at hig h levels in normal myeloid precursors and in acute myeloid leukemias ( AMLs) which are clonal derivatives of myeloid precursors that have los t the ability to differentiate into mature blood cells, Two MPO allele s differ at -463 G/A within a cluster of nuclear receptor binding site s in an Alu element. The -463 G creates a stronger SP1 binding site an d retinoic acid (RA) response element (RARE) in the allele termed Sp. In this study, we investigate potential links between MPO genotype, MP O expression level, and myeloid leukemia, The SpSp MPO genotype is sho wn to correlate with increased MPO mRNA levels in primary myeloid leuk emia cells. This higher expressing SpSp genotype is further shown to b e overrepresented in acute promyelocytic leukemia-M3 (APL-M3) and AML- M4, suggesting that higher levels of MPO are associated with an increa sed risk for this subset of leukemias, (C) 1997 by The American Societ y of Hematology.