BCR signaling contributes to autophagy regulation in chronic lymphocytic leukemia

B-cell receptor signaling induces proteasomal degradation of PDCD4 via MEK1/2 and mTORC1 in malignant B cells

“…Dysregulation of mRNA translation is a common feature in cancer, including lymphoma and leukemia, and targeted inhibition of translation is an exciting new area of drug discovery [46] , [47] . We showed previously that activation of signaling downstream of sIgM in CLL cells resulted in down-regulation of PDCD4 (and up-regulation of its target for inhibition, eIF4A) [23] .…”

Human pluripotent stem cells identify molecular targets of trisomy 12 in chronic lymphocytic leukemia patients

“…tri12 CLL has previously been shown to possess unique properties (Abruzzo et al, 2018;Autore et al, 2019;Beekman et al, 2018;Bulian et al, 2017;Decker et al, 2012;Fiorcari et al, 2019;Vendramini et al, 2019;Zucchetto et al, 2013), but targeted therapies have not arisen. Tumor microenvironment (Cutrona et al, 2018), B cell receptor (BCR) signaling (Smith et al, 2020), and epigenetic regulation (Gaiti et al, 2019) are important considerations that affect CLL disease pathogenesis. These factors, in addition to treatment history and patient background, may contribute to the difficulty in target identification using CLL patient-derived cells.…”

Targeting Autophagy Triggers Apoptosis and Complements the Action of Venetoclax in Chronic Lymphocytic Leukemia Cells

“…The BTK/Akt/mTOR pathway is another crossroads between the BCR pathway and autophagy. It has been shown that inhibition of BCR-mediated autophagy using the Vsp34 inhibitor VPS34-IN1 augmented the action of venetoclax in CLL [ 13 ]. Contrary to mTOR, the AMPK pathway has been less investigated in CLL; however, it has recently been implicated in energy reprogramming of venetoclax-resistant lymphoma cells [ 14 ].…”