Work

Insulin-like growth factor-1 receptor participates in the anti-MDS action involving the MICA/B-NKG2D axis

Year: 2026

Type: article

Abstract: Purpose Myelodysplastic syndromes (MDS) represent a clonal malignancy of the hematopoietic system with a high risk of progression to acute myeloid leukemia (AML). Patients with MDS commonly exhibit natural killer (NK) cell dysfunction, impairing their ability to effectively eliminate malignant cells and posing a serious health threat. The key to treating MDS and preventing its progression to AML lies in restoring and activating NK cell killing functions while eliminating malignant cells, thereby establishing immune interactions between MDS cells and NK cells. Method We screened the bone marrow of three patients with primary MDS and three patients with MDS converted to AML for relevant differential genes by Nanostring technology and screened for IGF-1R. We explored the potential and mechanisms of targeting IGF-1R in the treatment of MDS by flow cytometry, immunofluorescence, Western blot, and cell co-culture techniques. Results Nanostring sequencing results showed differential expression of IGF-1R in bone marrow cells from MDS patients and trans-AML patients. Differential expression was found to be concentrated on CD34+ cells by flow cytometry. Inhibition of IGF-1R induced DNA damage in MDS cell lines SKM-1 and KG-1, upregulated MICA/B on the surface of MDS cells, and enhanced NK cell-mediated killing of MDS cells, consistent with the involvement of the MICA/B–NKG2D axis. Conclusion IGF-1R is involved in the genesis and development of MDS and may modulate the interaction between MDS cells and NK cells, thus serving as a potential target for MDS therapy.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1960550