By using a cDNA clone of the myeloperoxidase (MPO) gene, we have studied, by Northern blot analysis, the level of MPO mRNA in eight cases of acute lymphoblastic leukemia (ALL).
Furthermore, the present case indicates the existence of a new form of ALL is characterized by MPO-positive granules detectable by ultracytochemistry and lymphoid-associated surface markers.
MPO mRNA expression in ALL cells was significantly associated with age < 1 year: leukemic blast cells from all five infant ALL patients expressed MPO mRNA, compared to five out of 21 ALL patients > 1 year of age whose leukemic cells were MPO mRNA(+) (p < 0.01).
The remaining seven cases were Ph negative at the cytogenetic and molecular levels; the leukemic blasts were MPO mRNA negative, confirming the lack of MPO gene expression in de novo ALL.
Western blot analysis using the pMPO antibody showed the expected 55-kd band for myeloperoxidase in pMPO-positive and pMPO-negative ALLs, suggesting a lack of specificity of this antibody in ALL.
The genetic contribution to the development of ALL is examined by association studies that analyze the loci of Phase I enzymes (cytochrome P-450, myeloperoxidase) and Phase II enzymes (quinone-oxidoreductase, glutathione-S-transferase, N-acetyltransferase).
However, when the wild-type MPO allele was considered together with the CYP2E1 and NQO1 risk-elevating genotypes, the risk of ALL was increased further (OR = 5.4, 95%CI, 1.2-23.4) suggesting a combined effect.