Transforming growth factor-beta and multidrug resistance in chronic lymphocytic leukemia

Patients with chronic lymphocytic leukemia (CLL) frequently respond to initial treatment, but then become resistant to chemotherapy. Studies have shown one important cause of chemotherapeutic resistance to be multidrug resistance (MDR). To investigate the potential role of MDR and transforming growth factor-beta (TFG-beta), a potent growth inhibitor of B lymphocytes, in the development of chemotherapeutic resistance in CLL, we evaluated 22 CLL patients for loss or mutation of TGF-beta receptors (TbetaR), plasma TGF-beta1 levels, and expression of MDR1 mRNA. Receptor crosslinking and immunoprecipitation experiments did not demonstrate loss of TbetaRs in any patients studied. No relationship between plasma TGF-beta1 levels and expression of MDR1 mRNA was seen. Correlation of plasma TGF-beta1 levels to disease stage revealed a consistent decline in plasma TGF-beta1 levels with advancing disease stage (P = 0.031).