title: De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes.
abstract: The interaction between the bone marrow microenvironment and malignant hematopoietic cells can result in the protection of leukemia cells from chemotherapy in both myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We, herein, characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with MDS, AML with myelodysplasia-related changes (MRC), a well-recognized clinical subtype of secondary AML, and de novo AML. We observed a significant inhibitory effect of MDS-MSC on T lymphocyte proliferation and no significant differences in any of the cytokines tested. AML-MSC inhibited T-cell proliferation only at a very low MSC/T cell ratio. When compared to the control, AML-MRCderived MSC presented a significant increase in IL6 expression, whereas de novo AML MSC presented a significant increase in the expression levels of VEGFA, CXCL12, RPGE2, IDO, IL1β, IL6 and IL32, followed by a decrease in IL10 expression. Furthermore, data indicate that IL-32 regulates stromal cell proliferation, has a chemotactic potential and participates in stromal cell crosstalk with leukemia cells, which could result in chemoresistance. Our results suggest that the differences between AML-MRC and de novo AML also extend into the leukemic stem cell niche and that IL-32 can participate in the regulation of the bone marrow cytokine milieu.
authors.affiliation: Hematology and Transfusion Medicine Center - University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Matheus Rodrigues
authors.initials: MR
authors.lastname: Lopes
authors.affiliation: Hematology and Transfusion Medicine Center - University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: João Kleber Novais
authors.initials: JK
authors.lastname: Pereira
authors.affiliation: Hematology and Transfusion Medicine Center - University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Paula
authors.initials: P
authors.lastname: de Melo Campos
authors.affiliation: Hematology and Transfusion Medicine Center - University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: João Agostinho
authors.initials: JA
authors.lastname: Machado-Neto
authors.affiliation: Hematology and Transfusion Medicine Center - University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.|Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Traina
authors.affiliation: Hematology and Transfusion Medicine Center - University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Sara T Olalla
authors.initials: ST
authors.lastname: Saad
authors.affiliation: Hematology and Transfusion Medicine Center - University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.|Department of Biological Sciences, Federal University of São Paulo, Diadema, São Paulo, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Favaro
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002460:Cell Line; D049109:Cell Proliferation; D060833:Cellular Microenvironment / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology; D003561:Cytarabine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D056747:Immunomodulation; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: D000964:Antimetabolites, Antineoplastic; D016207:Cytokines; D035683:MicroRNAs; D016328:NF-kappa B; D003561:Cytarabine; D020928:Mitogen-Activated Protein Kinases