IFM is a Potential Key Player in AML Cell Survival and CML Cell Resistance to Tyrosine Kinase Inhibitor

Abstract

Myeloid leukemia is characterized by the excessive proliferation of myeloid cells within the bone marrow. It is categorized into acute (AML) and chronic (CML) myeloid leukemia, with distinct etiologies and therapeutic complexities. The genetic heterogeneity of AML contributes to varying treatment responses, leading to a high mortality rate. One gene that has been identified as an adverse prognostic factor in AML is IFM, although its exact role remains unelucidated. IFM belongs to the group of IFN- related DNA damage-resistant signature (IRDS) genes, which is associated with resistance to DNA- damaging therapies across various types of cancer. However, the involvement of IRDS genes, particularly IFM, in tyrosine kinase inhibitor (TKI) resistance in CML remains unclear. Thus, this study sought to investigate the impact of IFM on AML cell survival and its expression level in TKI-resistant CML cells in vitro. It was observed that IFM knockdown induced apoptosis in AML cells due to the elevation in DNA damage level. Moreover, IFM expression is induced in TKI-resistant CML cells, indicating its potential role in TKI resistance. These findings suggest a pro-tumoral role for IFM in both acute and chronic myeloid leukemia.