THE ROLE OF LET-7/HMGA2 LINKAGE IN THE PATHOGENESIS AND PROGNOSIS OF MYELODYSPLASTIC NEOPLASMS

Abstract

Introduction: MicroRNAs (miRNAs),are significant regulators of human hematopoietic stem cells. Their deregulation contributes to hematological malignancies.The let-7 family has been found frequently deregulated in malignancies.In MDS various alterations of miRNAs have been reported.High Mobility Group AT-Hook 2 (HMGA2) protein functions as a transcriptional regulator. In this study, we investigated the HMGA2 expression in MDS and specifically in patients with fibrosis we studied the prognostic significance of four members of the let-7 family (let-7a, let-7b, let-7c, let-7d). Methods: RNA extraction, reverse transcription, anda SYBR Green based real-time PCR were performed for the absolute quantification of HMGA2, using standard protocols. After RNA polyadenylation and reverse transcription with an oligo-dT adapter primer, miRNAs transcript levels were determined using the SYBR Green chemistry. IBM SPSS statistics, version 26 (IBM Corporation, North Castle, NY, USA) was used for the analysis. Results: HMGA2 gene expression was investigated in 78 patients with MDS, whereas transcript levels of four members of the let-7 family (let-7a, let-7b, let-7c, let-7d) were analyzed in 11 patients with fibrosis. Let-7a transcript levels were significantly higher in MDS patients who developed acute myeloid leukemia (AML) compared to the group that did not (p=0.0141). Let-7d presented a negative correlation (p=0.0408). A moderate (p =0.0483) negative correlation of HMGA2 with let-7c, and a strong positive correlation (p =0.0481) with let-7d, were observed. Conclusions: In literature, the let-7/HMGA2 linkage could be a signature in MDS pathogenesis. Let-7a level was found higher in transformation to AML,defining it as a poor prognostic factor, in contrast with the protective role of high let-7d.