Our bioinformatics analysis revealed the enrichment of UPR genes in NT1-M CLL cells, mostly involving the PERK branch, such as ATF4 and CHOP. In keeping with these data, we demonstrated that PGA1 cells overexpressing mutation of NOTCH1 showed an increase in ATF4 and CHOP gene expression when compared with PGA1 cells transduced with the empty vector and with NT1-WT. Here, EIF2AK3 is linked to B-cell chronic lymphocytic leukemia.