The NF-κB subunit Rel A is associated with in vitro survival and clinical disease progression in chronic lymphocytic leukemia and represents a promising therapeutic target

摘要: In this study, we characterized nuclear factor κB (NF-κB) subunit DNA binding in chronic lymphocytic leukemia (CLL) samples and demonstrated heterogeneity basal inducible NF-κB. However, all cases showed higher NF-κB than normal B cells. Subunit analysis revealed of p50, Rel A, c-Rel primary CLL cells, A was associated with vitro survival ( P = .01) high white cell count shorter lymphocyte doubling time .01). induction after stimulation anti-IgM increased < .001) expression the signaling molecule ZAP-70 .003). Prompted by these data, evaluated novel parthenolide analog, LC-1, 54 patient samples. LC-1 induced apoptosis tested a mean LD50 2.8 μM 24 hours; T cells were significantly more resistant to its apoptotic effects .001). Apoptosis preceded marked loss sensitivity correlated .03, r2 0.15). Furthermore, inversely fludarabine .001, 0.3), implicating resistance. Taken together, data indicate that represents an excellent therapeutic target for incurable disease.