RESUMO
We analyzed multipotent mesenchymal stromal cells (MMSCs) from the bone marrow (BM) of 33 acute myeloid leukemia (AML) patients at diagnosis, after the first course of chemotherapy (day 37), and at days 100 and 180 after diagnosis. All patients were treated according to the AML 01.10 protocol. Cumulative production of MMSCs from AML patients at diagnosis was normal but increased during treatment. Most of the studied genes were upregulated at AML diagnosis, some (IL6, IL1B, LIF) remained upregulated during treatment, and others were downregulated (FGFR1, ICAM1) or normalized. A few genes were normal at diagnosis but decreased during treatment (FGF2, FGFR2, VEGF, SDF1, SOX9, TGFB1). The upregulation of proinflammatory genes both at diagnosis and during remission reflects ongoing inflammation. PDGFRB expression was upregulated in MMSCs from patients in relapse versus those in remission. The AML 01.10 protocol downregulates the expression of genes related to proliferation, differentiation and niche formation.
Assuntos
Medula Óssea/patologia , Leucemia Mieloide Aguda/diagnóstico , Células-Tronco Mesenquimais/metabolismo , Microambiente Tumoral , Adulto , Biomarcadores , Estudos de Casos e Controles , Proliferação de Células , Gerenciamento Clínico , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/terapia , Masculino , Células-Tronco Mesenquimais/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Transdução de Sinais , Fatores de TempoRESUMO
Bone marrow (BM) derived adult multipotent mesenchymal stromal cells (MMSCs) and fibroblast colony-forming units (CFU-Fs) of 20 patients with acute myeloid leukemia (AML) and 15 patients with acute lymphoblastic leukemia (ALL) before and during 1 year after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) were studied. The growth characteristics of MMSCs of all patients before allo-HSCT were not altered; however, relative expression level (REL) of some genes in MMSCs, but not in CFU-Fs, from AML and ALL patients significantly changed. After allo-HSCT, CFU-F concentration and MMSC production were significantly decreased for 1 year; REL of several genes in MMSCs and CFU-F-derived colonies were also significantly downregulated. Thus, chemotherapy that was used for induction of remission did not impair the function of stromal precursors, but gene expression levels were altered. Allo-HSCT conditioning regimens significantly damaged MMSCs and CFU-Fs, and the effect lasted for at least 1 year.