1 research outputs found
Fludarabine and Cladribine Induce Changes in Surface Proteins on Human B‑Lymphoid Cell Lines Involved with Apoptosis, Cell Survival, and Antitumor Immunity
Fludarabine and cladribine are purine analogues used
to treat hematological
malignancies. Alone or in combination with therapeutic antibodies,
they are effective in treating patients with chronic lymphocytic leukemia
and non-Hodgkin's lymphoma. However, the mechanisms of action of these
drugs are not well understood. Plasma membrane proteins perform a
variety of essential functions that can be affected by malignancy
and perturbed by chemotherapy. Analysis of surface proteins may contribute
to an understanding of the mechanisms of action of purine analogues
and identify biomarkers for targeted therapy. The surface of human
cells is rich in N-linked glycoproteins, enabling use of a hydrazide-coupling
technique to enrich for glycoproteins, with iTRAQ labeling for quantitative
comparison. A number of plasma membrane proteins on human leukemia
and lymphoma cells were affected by treatment with a purine analogue,
including decreases in CD22 (an adhesion and signaling molecule) and
increases in CD205 (a “damaged cell marker”) and CD80
and CD50 (T-cell interaction molecules). Purine analogues may affect
B-cell receptor (BCR) signaling and costimulatory molecules, leading
to multiple signals for apoptosis and cell clearance. Fludarabine
and cladribine induce differential effects, with some cell survival
proteins (ECE-1 and CD100) more abundant after fludarabine treatment.
Cell surface proteins induced by fludarabine and cladribine may be
targets for therapeutic antibodies