Tetrahydrofolate dehydrogenase cytochemistry in acute lymphoblastic leukemia

We studied the cytochemical distribution of tetrahydrofolate dehydrogenase (FH4D), an enzyme involved in nucleic acid metabolism and thus in cell proliferation and differentiation processes, in bone marrow blasts from 37 cases of acute lymphoblastic leukemia (ALL), of whom 23 were pediatric patients. 26 cases were analyzed at onset, 11 in relapse. The ALL cases were immunologically classified as T (10), common (20), B (3) and null (4). In each subgroup the majority of lymphoblasts were positive, with heterogeneous positivity patterns and variable degrees of enzyme activity. Most T lymphoblasts were characterized by focal localization of FH4D, whereas in common blasts reactivity - usually less strong - was either focally localized or scattered with several fine granules. Finally, many B and null blasts showed diffuse positivity. A quantitative evaluation of FH4D activity using cytophotometric technique (Vickers M86) demonstrated higher degrees of reactivity in leukemic blasts than in normal lymphocytes. Moreover, slightly different levels of reactivity were observed in relation to immunological phenotype, age and stage of the disease. Therefore we think that FH4D is a useful additional marker for ALL characterization.