THIS IS WHERE DISCOVERIES ARE BORN!

Researchers from the Medical University of Bialystok (Tomasz Pienkowski, Aleksandra Golonko, Lukasz Bolkun, Katarzyna Wawrzak-Pienkowska, Lukasz Szczerbinski, Adam Kretowski, Michal Ciborowski), in collaboration with Bialystok University of Technology (Włodzimierz Lewandowski and Renata Świsłocka) and the MD Anderson Cancer Center (Waldemar Priebe), have published an article titled “Investigation into biased signaling, glycosylation, and drug vulnerability of acute myeloid leukemia” in the journal Pharmacology & Therapeutics (Impact Factor 12). 

Understanding and harnessing biased signaling offers significant potential for developing new or improving existing therapeutic strategies. In acute myeloid leukemia (AML), where dysregulated signaling through GPCRs and RTKs contributes to disease progression and treatment resistance, selectively targeting specific signaling pathways may enhance therapeutic efficacy while reducing potential toxicity. 

The combination of biased signaling and glycosylation represents an innovative approach to drug design, allowing for selective activation of anti-cancer pathways while minimizing adverse effects and resistance. A key component of this process is glycosylation—a post-translational protein modification that shapes receptor conformation and regulates their function through specific glycan patterns. In AML, chemokine receptors such as CXCR4, which are often hyperglycosylated and overactive, are of particular interest as promising therapeutic targets. Glycosylation influences receptor activity and drug interactions, potentially supporting cancer cell survival or impairing treatment efficacy. 

Integrating glycosylation analysis with computational modeling, high-throughput screening, and modern drug delivery systems paves the way for personalized, more precise, and less toxic AML therapies. 

A comprehensive review of the literature suggests that understanding the interplay between glycosylation and biased signaling in AML may be crucial to developing more effective, targeted, and safer therapies, as well as overcoming treatment resistance. 

The research was funded by the PRELUDIUM grant entitled "Differences in the glycoproteomic profile of acute myeloid leukemia (AML) between cytogenetic and risk groups according to the European LeukemiaNet guidelines", awarded by the National Science Centre, Poland (2023/49/N/NZ5/01525). 

Link to the publication: Investigation into biased signaling, glycosylation, and drug vulnerability of acute myeloid leukemia