Non-T, non-B acute lymphocytic leukemia cells enhance the mitogen induced proliferation of normal lymphocytes

Peripheral blood and bone marrow mononuclear cells (MNC) from patients with untreated non-T, non-B acute lymphocytic leukemia (ALL) were assessed for capacity to respond to the mitogens phytohemagglutinin (PHA), pokeweed (PWM) and staphylococcal enterotoxin A (SEA). At low mitogen concentrations considerable reactivity was observed to PHA and SEA, but not to PWM by patient MNC including specimens comprised of at least 90% leukemic cells. The responding cells were identified in cell separation experiments and by surface marker analysis as residual normal T-cells. The non-T, non-B leukemic cells enhanced the mitogen induced proliferation of responding lymphocytes as determined by co-culture experiments in which 5 × 10³ or 10⁴ MNC from normal donors were cultured with feeder layers of 3 × 10⁵ mitomycin C treated MNC from autologous or unrelated normal donors or from ALL patients. In contrast to MNC feeder layers from normal donors, feeder layers of non-T, non-B leukemic cells enhanced normal lymphocyte reactivity to PHA and SEA but not to PWM as determined by ³H-thymidine uptake and cell survival. The potentiating effect of non-T, non-B leukemic cells was not mediated entirely by an allogeneic interaction as shown by the demonstration that frozen-thawed non-T, non-B leukemic cells enhanced the mitogen response of autologous MNC obtained during remission. Mitomycin treated feeder layers of leukemia cells from patients with acute myelogenous leukemia as well as bone marrow MNC from a normal donor or from lymphoma patients without bone marrow involvement failed to enhance PHA and SEA reactivity of normal lymphocytes. In addition, leukemia cells from patients with T-cell ALL did not potentiate normal lymphocyte reactivity in contrast to non-T, non-B ALL cells, providing a functional distinction between these two subtypes of ALL.