Deciphering the role of HMGA2 and let-7 microRNAs in myelodysplastic neoplasms with bone marrow fibrosis

Myelodysplastic neoplasms (MDS) are heterogeneous clonal disorders with increased risk of transformation to acute myeloid leukemia. The HMGA2 gene, a chromatin-binding regulator suppressed by the let-7 miRNA family, has been implicated in malignant transformation and fibrosis. In this study, HMGA2 was investigated in patients with MDS, while four members of the let-7 family (let-7a, let-7b, let-7c, let-7d) were specifically assessed in those with bone marrow fibrosis. HMGA2 showed no association with established prognostic scores or survival, while in MDS with bone marrow fibrosis, distinct let-7 patterns emerged: let-7a associated with cytopenias and reduced platelet counts, let-7c with blast percentage and ineffective hematopoiesis, while let-7d displayed a potentially protective profile with higher platelet count and fewer cytopenias. A novel positive correlation between HMGA2 and let-7d was also identified. These findings suggest that let-7 miRNAs may serve as prognostic biomarkers and therapeutic targets in fibrotic MDS, whereas HMGA2 appears less predictive.