Genetic, phenotypic and clinical features of acute lymphoblastic leukemiasexpressing myeloperoxidase mRNA detected by RT-PCR

Myeloperoxidase (MPO) is found in the azurophilic granules of normal myeloc ytic cells. Cytochemical staining for MPO activity is used clinically to di stinguish myeloid from acute lymphoid leukemias (ALL). However, using a hig hly sensitive RT-PCR technique, it is possible to detect MPO mRNA in otherw ise clear ALL. The significance of this finding remains poorly understood. We have extended our observations to a series of 57 patients with the prima ry diagnosis of ALL (46 patients tested at diagnosis and 11 cases at relaps e). We identified 25 cases (43.8%) of MPO mRNA(+)/enzyme(-) ALL (17 B cell and eight T cell lineage). Expression of myeloid antigens (CD13 or CD33) we re detected in nine of them, and remarkably, 18 cases (72%) displayed CD34. Of these 25 MPO mRNA(+) leukemias, 10 (40%) are Bcr-Abl positive (with P21 0 fusion transcript in five patients while the five remaining cases carried P190 transcript). Moreover, 11 of 16 myeloid negative cases were also nega tive for any type of Bcr-Abl and MLL rearrangement, indicating that MPO mRN A positivity is not either invariably related to that chromosomal abnormali ty or necessarily associated with the presence of other myeloid differentia tion features. Interestingly, six of these 11 cases are T-ALL, suggesting t he presence of some overlapping phase for T and myeloid lineage commitment. Taken together, these findings could suggest a separate biological disease with immature origin and bipotential differentiation capability, which inv olves B and T-ALL subtypes and should lead to new investigations regarding their prognostic impact.