Blood: Bcl-2 member expresses changes that reveal CLL Venetok drug resistance mechanism

Chronic lymphocytic leukemia (CLL) cells circulate between lymph nodes (LN) and peripheral blood (PB), and members of the Bcl-2 family show significant swaying between these chambersSpecifically, Bcl-XL and Mcl-1, not targets for Bcl-2 inhibitor Vinatok, are expressed in LN for an increaseGiven that Ilutinib promotes the separation of CLL cells from LN, the researchers speculate that Ilutini may have affected the expression of Bcl-XL and Mcl-1 after the CLL cells were removed from LN, making TheC Cells sensitive to VinatokAs a result, the researchers studied the expression of members of the Bcl-2 family in patients treated with Ilutini or Vinatok, and parsed the functional interactions of Bcl-2 family members in in an in vitro model of Vinatok drug resistancein the PB, the expression levels of Bcl-XL and Mcl-1 in cells that have just migrated from LN are higher than those of the cells that migrate LNWhen Ilutinib was treated, the difference disappeared, and in particular, in patients who relapsed after Ilutinib treatment, the difference recursbut the early increase in bcl-2 family members during the veneertok treatment suggests that the two drugs act differentlyIn CLL cells that are completely resistant to Vinatok (caused by Bcl-XL, McL-1 and Bfl-1 induction led by CD40), the BH3 analog was used for spectral analysisThe double or triple combinations of several BH3 simulations have a high degree of synergy in restoring the lethal effect of CLL cellsfinally, the researchers confirmed that the apoptotic protein Bim interacts in a certain order with members of the anti-apoptosis Bcl-2: Bcl-XL-Mcl-1 Bfl-1, this study shows that Bcl-XL plays a more important role in Vinatok resistance than Mcl-1, providing a biological basis for potential synergies between Irutini and Vinatok