Browsing by Subject "Acute myeloid leukaemia"

Now showing 1 - 4 of 4
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    DPP4+ exosomes in AML patients’ plasma suppress proliferation of hematopoietic progenitor cells
    (Springer Nature, 2021) Namburi, Swathi; Broxmeyer, Hal E.; Hong, Chang-Sook; Whiteside, Theresa L.; Boyiadzis, Michael; Microbiology and Immunology, School of Medicine
    Mechanisms by which acute myeloid leukemia (AML) interferes with normal hematopoiesis are under intense investigation. Emerging evidence suggests that exosomes produced by leukemia blasts suppress hematopoiesis. Exosomes isolated from AML patients' plasma at diagnosis significantly and dose-dependently suppressed colony formation of normal hematopoietic progenitor cells (HPC). Levels of HPC suppression mediated by exosomes of AML patients who achieved complete remission (CR) were significantly decreased compared to those observed at AML diagnosis. Exosomes from plasma of patients who had achieved CR but with incomplete cell count recovery (CRi) after chemotherapy suppressed in vitro colony formation as effectively as did exosomes obtained at AML diagnosis. Dipeptidylpeptidase4 (DPP4/CD26), a serine protease that cleaves select penultimate amino acids of various proteins, has been previously implicated in the regulation of hematopoiesis. DPP4 was carried by exosomes from AML plasma or leukemia cell lines. Leukemia exosomes which suppressed HSC colony formation had markedly higher DPP4 functional activity than that detected in the exosomes of normal donors. Pharmacological inhibition of DPP4 activity in AML exosomes reversed the effects of exosome-mediated myelosuppression. Reversing the negative effects of exosomes on AML hematopoiesis, and thus improving cell count recovery, might emerge as a new therapeutic approach to AML.
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    Multifocal Myeloid Sarcomas: A Rare Presentation of AML
    (BMJ Publishing Group, 2017-10-04) Angsubhakorn, Natthapon; Suvannasankha, Attaya; Medicine, School of Medicine
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    Prognostic effect of gender on outcome of treatment for adults with acute myeloid leukaemia
    (Wiley, 2021) Wiernik, Peter H.; Sun, Zhuoxin; Cripe, Larry D.; Rowe, Jacob M.; Fernandez, Hugo F.; Luger, Selina M.; Lazarus, Hillard M.; Paietta, Elisabeth M.; Tallman, Martin S.; Litzow, Mark R.; Medicine, School of Medicine
    There are conflicting reports in the literature suggesting that one gender or the other has a better survival with acute myeloid leukaemia (AML). This study was done in an attempt to resolve the issue. The effect of gender was examined on 3,546 newly diagnosed patients with AML, including 548 patients with acute promyelocytic leukaemia (APL) enrolled in 10 multi-institutional treatment studies from March 1984 to November 2008. Kaplan-Meier estimates were used to estimate event-time distributions for survival and multivariate models were used to examine the gender effect after adjusting for multiple risk factors. P values were based on 2-sided tests. Non-APL female patients had a significantly better overall but not disease-free survival than males, irrespective of age, initial WBC count, or dose of daunorubicin. No differences were observed for obese or FLT3-ITD + patients. Female APL patients had a significantly better overall and disease-free survival than male APL patients, and differences in survival were greater for patients with t(15;17) + other cytogenetic abnormalities compared with those with t(15;17) only. Gender is an independent prognostic variable in patients with AML. Whether these survival differences are due to hormonal, genetic or pharmacokinetic differences between the sexes, or differential toxin exposure such as smoking is unknown. However, the former seems less likely since patient age did not influence the survival advantage for female patients.
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    Targets for chimeric antigen receptor T-cell therapy of acute myeloid leukemia
    (Frontiers Media, 2022-12-20) Schorr, Christopher; Perna, Fabiana; Medicine, School of Medicine
    Acute Myeloid Leukemia (AML) is an aggressive myeloid malignancy associated with high mortality rates (less than 30% 5-year survival). Despite advances in our understanding of the molecular mechanisms underpinning leukemogenesis, standard-of-care therapeutic approaches have not changed over the last couple of decades. Chimeric Antigen Receptor (CAR) T-cell therapy targeting CD19 has shown remarkable clinical outcomes for patients with acute lymphoblastic leukemia (ALL) and is now an FDA-approved therapy. Targeting of myeloid malignancies that are CD19-negative with this promising technology remains challenging largely due to lack of alternate target antigens, complex clonal heterogeneity, and the increased recognition of an immunosuppressive bone marrow. We carefully reviewed a comprehensive list of AML targets currently being used in both proof-of-concept pre-clinical and experimental clinical settings. We analyzed the expression profile of these molecules in leukemic as well normal tissues using reliable protein databases and data reported in the literature and we provide an updated overview of the current clinical trials with CAR T-cells in AML. Our study represents a state-of-art review of the field and serves as a potential guide for selecting known AML-associated targets for adoptive cellular therapies.