Dual investigation of Myeloid and Lymphoid compartments: role of miRNAs in MDS and HOXA9 in B-ALL

Here we report an exploration of uncommonly investigated molecules in these diseases, microRNA in MDS, and HoxA9 in B-ALL. miRNAs are small non-coding RNAs that regulate gene expression and are linked to cancer development and progression. MDS with an increased risk of AML progression are managed using hypomethylating agents(azacytidine), alone or in conjunction with other drugs. miRNA expression of 26 high-risk MDS-patients treated with azacytidine and lenalidomide, at baseline and during therapy, were analyzed. miR-192-5p was discovered as differentially expressed during therapy response. Patients were clustered in responder, non-responder, and early losing-response and showed a different expression of this miRNA, as well as of its target BCL2. This investigation also revealed a significant association between miR-192-5p levels during the therapy and extended Overall Survival (OS) and Leukemia-Free Survival (LFS) in responder patients. On the ALL side, HoxA9 is a member of the Hox-gene family. Dysregulated expression of HoxA9 has been associated with leukemia, where is commonly upregulated. A recent publication revealed a significant downregulation of HoxA9 mRNA levels in leukemic murine samples when compared with normal B-cell precursors. This was highly surprising, because HoxA9 is an oncogene involved in AML, T-ALL, and B-ALL with MLL rearrangement, and led to speculate on tumor suppressive role of this gene in IL7R mutant B-ALL. Proliferation on human cell lines was then assessed and the result was a proliferative disadvantage associated with HoxA9 overexpression. The downregulation mechanism was then investigated, evaluating on mice-derived leukemic cells the effect of SAHA. The aim of this dual investigation of miRNA in MDS and HoxA9 in B-ALL is to increase the understanding of the intricate web of molecular events that drive these hematological malignancies, ultimately striving for improved patient management and outcome.