PELI1 Identified as Key Target to Overcome Resistance in Chronic Myeloid Leukemia

Chronic Myeloid Leukemia (CML) is driven by the BCR-ABL1 fusion gene. New research reveals that the protein PELI1 is a central regulator of this disease, protecting BCR-ABL1 from degradation and promoting cancer cell growth.

Scientists found that BCR-ABL1 itself upregulates PELI1 through the STAT5 and FOXP3 pathway. PELI1 then interacts directly with BCR-ABL1, shielding it from breakdown within leukemia cells. This dual role makes PELI1 an active contributor to both maintaining the oncogene and driving disease progression.

Critically, inhibiting PELI1-either genetically or pharmacologically-suppressed cancer cell growth in both TKI-sensitive and TKI-resistant CML cells. This approach also effectively targeted leukemia stem cells, which are often responsible for disease relapse.

These findings position PELI1 as a promising new therapeutic target to overcome resistance and improve outcomes in CML.