12 research outputs found
Ponatinib for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia
38 - Enasidenib (AG-221), A Selective Oral Inhibitor of Mutant Isocitrate Dehydrogenase 2 (IDH2) Enzyme, In Patients with Myelodysplastic Syndromes (MDS)
High Expression Level of SP1, CSF1R, and PAK1 Correlates with Sensitivity of Leukemia Cells to the Antibiotic Mithramycin
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PS1025 IVOSIDENIB (AG-120) INDUCES DURABLE REMISSIONS AND TRANSFUSION INDEPENDENCE IN PATIENTS WITH IDH1-MUTANT NEWLY-DIAGNOSED AML: UPDATED RESULTS FROM A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY
Acute myeloid leukaemia niche regulates response to L-asparaginase
Eradicating the malignant stem cell is the ultimate challenge in the treatment of leukaemia. Leukaemic stem cells (LSC) hijack the normal haemopoietic niche, where they are mainly protected from cytotoxic drugs. The anti‐leukaemic effect of L‐asparaginase (ASNase) has been extensively investigated in acute lymphoblastic leukaemia, but only partially in acute myeloid leukaemia (AML). We explored the susceptibility of AML‐LSC to ASNase as well as the role of the two major cell types that constitute the bone marrow (BM) microenvironment, i.e., mesenchymal stromal cells (MSC) and monocytes/macrophages. Whilst ASNase was effective on both CD34+CD38+ and CD34+CD38− LSC fractions, MSC and monocytes/macrophages partially counteracted the effect of the drug. Indeed, the production of cathepsin B, a lysosomal cysteine protease, by BM monocytic cells and by AML cells classified as French‐American‐British M5 is related to the inactivation of ASNase. Our work demonstrates that, while MSC and monocytes/macrophages may provide a protective niche for AML cells, ASNase has a cytotoxic effect on AML blasts and, importantly, LSC subpopulations. Thus, these features should be considered in the design of future clinical studies aimed at testing ASNase efficacy in AML patients