Cell Death Differ: Atypical NF-B signal transducting paths affect the resistance of chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a malignant tumor that is originally produced in hematostogenic tissue, and one of its main problems is the endogenesitive resistance to treatment.
, although new targeted therapies have been found and developed, recurrence of diseases is still common.
in CLL, the lymph node (LN) micro-environment transmits critical survival signals by inducing the expression of anti-apoptosis Bcl-2 members Bcl-XL, Bfl-1, and Mcl-1, leading to apoptosis blocking.
also makes the CLL highly sensitive to the Bcl-2 inhibitor Venetoclax (Venetok, ABT-199).
, however, only a very small number of patients achieved complete remission, which may be associated with micro-environmentally induced resistance.
Since the actual regulation of CLL Bcl-XL in LN microencology is not yet known, it is necessary to gain insight into the relevant signals that induce Bcl-XL expression to evaluate alternatives to targeted treatment in CLL and other pathology.
evaluated the signals that drive Bcl-XL expression in a variety of candidate LN signals.
Bcl-XL plays an important role in CLL's venetoclax resistance Researchers have found that CD40-induced NF-B signal transducting paths dominate, which also leads to the activation of both classical and non-classical NF-B signal paths.
confirmed that the expression of Bcl-XL was first induced by the classic NF-B approach, then stabilized by NIK and enhanced and maintained by non-classical NF-B signals.
NF-B sub-base p65 and p52 can be combined with the starter region of Bcl-XL and transcription is activated after CD40 stimulation.
addition, further studies have shown that the classic NF-B signal transducting path is associated with the level of expression of Bfl-1, while McL-1 is not regulated by NF-B transcription.
, the researchers selectively inhibited non-classical NF-B signaling paths by targeting NIK's new compounds, and found that Venetoclax drug-resistant CLL cells were resensitive to Venetoclax.
overall, by targeting atypical NF-B signal paths to reduce the expression of Bcl-XL and increase the sensitivity of venetoclax, the results show that CLL tends to be sensitive to apoptosis by targeting non-classical NF-B signal transducts.