دورية أكاديمية

Adrenomedullin Expression Characterizes Leukemia Stem Cells and Associates With an Inflammatory Signature in Acute Myeloid Leukemia

التفاصيل البيبلوغرافية
العنوان: Adrenomedullin Expression Characterizes Leukemia Stem Cells and Associates With an Inflammatory Signature in Acute Myeloid Leukemia
المؤلفون: Simonetti, Giorgia, Angeli, Davide, Petracci, Elisabetta, Fonzi, Eugenio, Vedovato, Susanna, Sperotto, Alessandra, Padella, Antonella, Ghetti, Martina, Ferrari, Anna, Robustelli, Valentina, Di Liddo, Rosa, Conconi, Maria Teresa, Papayannidis, Cristina, Cerchione, Claudio, Rondoni, Michela, Astolfi, Annalisa, Ottaviani, Emanuela, Martinelli, Giovanni, Gottardi, Michele
المصدر: Frontiers in Oncology ; volume 11 ; ISSN 2234-943X
بيانات النشر: Frontiers Media SA
سنة النشر: 2021
المجموعة: Frontiers (Publisher - via CrossRef)
مصطلحات موضوعية: Cancer Research, Oncology
الوصف: Adrenomedullin (ADM) is a hypotensive and vasodilator peptide belonging to the calcitonin gene-related peptide family. It is secreted in vitro by endothelial cells and vascular smooth muscle cells, and is significantly upregulated by a number of stimuli. Moreover, ADM participates in the regulation of hematopoietic compartment, solid tumors and leukemias, such as acute myeloid leukemia (AML). To better characterize ADM involvement in AML pathogenesis, we investigated its expression during human hematopoiesis and in leukemic subsets, based on a morphological, cytogenetic and molecular characterization and in T cells from AML patients. In hematopoietic stem/progenitor cells and T lymphocytes from healthy subjects, ADM transcript was barely detectable. It was expressed at low levels by megakaryocytes and erythroblasts, while higher levels were measured in neutrophils, monocytes and plasma cells. Moreover, cells populating the hematopoietic niche, including mesenchymal stem cells, showed to express ADM . ADM was overexpressed in AML cells versus normal CD34 + cells and in the subset of leukemia compared with hematopoietic stem cells. In parallel, we detected a significant variation of ADM expression among cytogenetic subgroups, measuring the highest levels in inv(16)/t(16;16) or complex karyotype AML. According to the mutational status of AML-related genes, the analysis showed a lower expression of ADM in FLT3 -ITD, NPM1 -mutated AML and FLT3 -ITD/ NPM1 -mutated cases compared with wild-type ones. Moreover, ADM expression had a negative impact on overall survival within the favorable risk class, while showing a potential positive impact within the subgroup receiving a not-intensive treatment. The expression of 135 genes involved in leukemogenesis, regulation of cell proliferation, ferroptosis, protection from apoptosis, HIF-1α signaling, JAK-STAT pathway, immune and inflammatory responses was correlated with ADM levels in the bone marrow cells of at least two AML cohorts. Moreover, ADM was upregulated in CD4 + T and ...
نوع الوثيقة: article in journal/newspaper
اللغة: unknown
DOI: 10.3389/fonc.2021.684396
DOI: 10.3389/fonc.2021.684396/full
الإتاحة: https://doi.org/10.3389/fonc.2021.684396Test
حقوق: https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.6914AF
قاعدة البيانات: BASE