Expression of GD3 Ganglioside in Childhood T-Cell Lymphoblastic Malignancies1

Lymphoblasts from seven children with T-cell lymphoblastic malig nancies and three children with non-T, non-B acute lymphoblastic leu kemia (ALL) were analyzed for ganglioside content. Nonmalignant I cells from thymus served as controls. Both ganglioside and glycoprotein sialic acid were increased approximately 3-3.5-fold in T-cell disease compared to thymic tissue when expressed on a per cell basis, but not on a per milligram protein basis. Thin-layer chromatography of the isolated ganglioside fraction from T-cell lymphoblasts revealed two major resorcinol-positive bands. One ganglioside comigrated with lI'-a-/V-acetylneuraminosyllactosylceramide (GM3), the major ganglioside in normal lymphoid tissue, and the other ganglioside comigrated with authentic II3o-A'-acetylneuraminosyl-a2—»8-jV-acetylneuraminosyllactosylceramide (GDj) in three different solvent systems. Neuraminidase treatment of the latter ganglioside yielded ( ;M <and lactosyl ceramide, hydrolysis products of (. 1),. Scanning densitometry revealed that whereas thymus cells con tained 97% CM] and 3% CD*, T-cell lymphoblasts contained from 22 to 86% GD3 and a corresponding decrease in GM3. The shift to increased GDj was observed in the blasts from all seven T-cell patients, but not in the blasts from the non-T, non-B patients studied. Only trace quantities of <.1) i were detected from two continuous T-ALL cell lines, HSB2 and Kl'MI 8402. The results demonstrate a consistently significant increase in ganglioside GD3 in uncultured, patient-derived T-cell ALL lympho blasts when compared to non-T-cell ALL and normal lymphoid tissue. Therefore, GD3 may represent a tumor-associated antigen for the T-cell subclass of childhood lymphoblastic malignancy.