miR-125b controls monocyte adaptation to inflammation through mitochondrial metabolism and dynamics

Introduction: The 2008 World Health Organization classification recognized a unique overlap category that combines features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). The least well characterized of the 4 overlap diseases is a rare entity known as MDS/MPN Unclassifiable (MDS/MPN-U), comprising Methods: We identified MDS/MPN-U patients within the Moffitt MDS database, baseline characteristics were reviewed, and responses to HMA utilizing IWG 2006 response criteria were assessed. The Kaplan-Meier method was applied to estimate overall survival (OS). Results: Among 127 patients with MDS/MPN-U, 62 patients received HMA treatment. There was no difference in baseline characteristics among those who received HMA or not, except that those treated with HMA were less likely to have low risk disease by IPSS, MD Anderson model or very low risk by revised IPSS (R-IPSS). Among 16 patients who had NextGen sequencing data, the 5 most common mutations were ASXL-1 (56%), TET2 (31%), JAK2 (33%), SRSF2 (25%), as well as SETBP1 , DNMT3A , and EZH2 (19%). The best overall response to HMA (hematological improvement [HI] or better) according to the International Working Group (IWG) 2006 criteria was 26%. Only 11 patients (low risk) underwent allogeneic stem cell transplant (allo-SCT) with no improvement or decrease in OS. The median OS was 33 months (mo). Among patients with IPSS low/int-1 risk disease, the median OS was 39 and 33 mo respectively for those treated with HMA vs. HMA untreated. (p=0.50). For Int-2/high risk IPSS, the median OS was 11 and 5 mo for those who received HMA and those who did not. (p=0.02). Based on R-IPSS the median OS for very low/low risk was 47 and 39 mo respectively for those treated with HMA and without (p=0.96), for intermediate risk, the median OS was 39 and 25 mo respectively (p 0.75), and for high and very high risk the median OS was 13 and 5 mo respectively for those treated with HMA and those who did not. (p Conclusions: Treatment with HMA is associated with modest improvement in OS among higher risk MDS/MPN-U, reinforcing the unmet need to improve outcomes in this group. Targeted therapy may prove to be of benefit as allo-SCT does not appear to be beneficial for patients even with low risk disease. Furthermore, these data demonstrate the need for prospective analysis of the outcomes of allo-SCT in patients with MDS/MPN-U to determine potential benefit to high risk patients. Disclosures Komrokji: Novartis: Consultancy, Speakers Bureau; Celgene: Membership on an entity9s Board of Directors or advisory committees, Research Funding.