Inhibiting YTHDF2 for B cell malignancies

Inhibiting YTHDF2, a dual RNA modification reader, could help treat B cell malignancies by decreasing the stability of m⁵C-modified transcripts encoding ATPase subunits, which promote ATP synthesis to fuel oncogenic transformation and proliferation, and also by increasing the stability of m⁶A-modified transcripts encoding tumor antigens, thus decreasing tumor antigen escape, immune evasion, and CAR T cell therapy resistance.

Bioinformatic analyses of public B cell malignancy patient datasets identified YTHDF2 as a top upregulated gene in B-ALL, and higher YTHDF2 mRNA expression correlated with shorter overall and progression-free survival. ...