Publications by authors named "M Balasis"
This work identifies MALAT1 as a requisite downstream effector of oncogenic feedforward inflammatory circuits necessary for the development of TET2-mutated CH and fulminant myeloid malignancy. We elucidate a novel mechanism by which MALAT1 "shields" p65 from dephosphorylation to potentiate this circuit and nominate MALAT1 inhibition as a future therapeutic strategy.
View Article and Find Full Text PDFPurpose: Preclinical studies in myeloid neoplasms have demonstrated efficacy of bromodomain and extra-terminal protein inhibitors (BETi). However, BETi demonstrates poor single-agent activity in clinical trials. Several studies suggest that combination with other anticancer inhibitors may enhance the efficacy of BETi.
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- * The study reveals three main differentiation trajectories for CMML cells: monocytic, megakaryocyte-erythroid progenitor (MEP), and normal-like, with the monocytic trajectory linked to negative outcomes and increased inflammation.
- * Hypomethylating agents can reduce monocytic-biased cells, and the research suggests that understanding these different states and their responses to therapies could lead to better treatments for patients with CMML and similar conditions.
Article Synopsis
- * Research shows that patients with both ASXL1 and NRAS mutations experience shorter leukemia-free survival compared to those with only ASXL1 mutations, and similar results were observed in mouse models which also exhibited aggressive disease progression.
- * NA-AML cells (from the mouse model) overexpress immune checkpoint ligands and show high MEK/ERK signaling activity, but combining treatments targeting MEK and BET can improve immune responses and extend survival
Article Synopsis
- The study investigates the effects of ruxolitinib, a JAK1/2 inhibitor, on patients with chronic myelomonocytic leukemia (CMML), a rare type of leukemia with no effective treatments, focusing on its potential to downregulate GM-CSF signaling.
- In a phase I/II clinical trial, 50 CMML patients were treated, along with 49 patient-derived xenografts (PDX) to assess the drug’s efficacy and safety, resulting in a clinical overall response rate of 38%.
- Results suggested that ruxolitinib is clinically effective with manageable side effects, and the study highlights the usefulness of PDX models in predicting patient responses, thereby validating its approach in investigating