The effects of Lin28a and its phosphorylation at S200 on Imatinib resistance in chronic myeloid leukemia

Abstract

Chronic myeloid leukemia (CML) is characterized by the fusion kinase Bcr-Abl. Patients are primarily treated with Imatinib, a tyrosine kinase inhibitor (TKI) targeting Bcr-Abl, but often encounter resistance after treatment. Previously, our laboratory established an Imatinib-resistant cell line which abnormally upregulated Lin28a. To assess whether Lin28a and its phosphorylation at S200 cause Imatinib resistance in CML, I overexpressed Lin28a, its phosphomimetic mutant Lin28aS200E, and their respective controls, empty vector and non-phosphorylatable mutant Lin28aS200A, in K562, EM2, and MOLM1 cell lines. Upon Imatinib treatment, these cells demonstrated little difference in their response. They also had similar sensitivity to other TKIs. The knockdown of Lin28a in ImR cells, however, slightly decreased the cell viability. These findings suggest that Lin28a and its phosphorylation are not sufficient to confer Imatinib resistance in CML. This study encourages further investigation into the molecular functions of Lin28a in CML and the underlying causes of Imatinib resistance.Quan My Quach, 202