Publications by authors named "N Dulphy"
Introduction: Acute myeloid leukemia (AML) is a rare haematological cancer with poor 5-years overall survival (OS) and high relapse rate. Leukemic cells are sensitive to Natural Killer (NK) cell mediated killing. However, NK cells are highly impaired in AML, which promote AML immune escape from NK cell immune surveillance.
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- Hematopoietic multipotent progenitors (MPPs) in the bone marrow can differentiate into various cell types, influenced by both intrinsic and extrinsic signals, with WHIM syndrome patients exhibiting an excess of myeloid cells due to CXCR4 signaling mutations.
- Research using knock-in mice with WHIM-associated mutations showed that MPP4 cells, which usually develop into lymphoid cells, instead skewed towards myeloid differentiation due to increased mTOR signaling and altered oxidative phosphorylation.
- Treatment with CXCR4 antagonist AMD3100 or mTOR inhibitor rapamycin reversed this myeloid bias, indicating that normal CXCR4 function is crucial for maintaining the lymphoid potential of MPP4 cells by regulating
Despite the advances in the understanding and treatment of myeloproliferative neoplasm (MPN), the disease remains incurable with the risk of evolution to acute myeloid leukemia or myelofibrosis (MF). Unfortunately, the evolution of the disease to MF remains poorly understood, impeding preventive and therapeutic options. Recent studies in solid tumor microenvironment and organ fibrosis have shed instrumental insights on their respective pathogenesis and drug resistance, yet such precise data are lacking in MPN.
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- Advancements in understanding myelodysplastic neoplasms (MDS) have revealed important cellular and molecular factors that influence disease progression, highlighting the significance of immune dysregulation in the bone marrow during MDS evolution.
- Despite these advancements, immunotherapy for MDS has lagged due to a lack of effective immune classifications for patient stratification and no widely accepted immune panels for clinical use.
- To address these challenges, the i4MDS consortium proposes standardized immune monitoring approaches, including flow cytometry panels and cytokine assays, aiming to improve patient stratification and develop predictive markers for treatment response in MDS.