RESUMO
It has been suggested that imatinib mesylate (IM) influences osteogenesis and bone turnover in treated patients. Here we show that the inhibitory effect of IM on cell multiplication is associated with an increased proportion of spliced osteocalcin (OCNs) in leukemia (HL-60) and osteosarcoma cells (MG-63, U-2 OS), despite a lower mRNA synthesis rate. In mouse osteoblastic MC3T3-E1 cells only OCNs is present, independently of treatment. As the stimulatory effect of IM on OCNs is also observed upon treatment with vitamin D, common regulatory processes may be considered.
Assuntos
Osteocalcina/genética , Osteocalcina/metabolismo , Piperazinas/farmacologia , Pirimidinas/farmacologia , Telomerase/metabolismo , Animais , Benzamidas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Células HL-60 , Humanos , Mesilato de Imatinib , Camundongos , Osteoblastos/metabolismo , Isoformas de Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Splicing de RNARESUMO
Transplantation of autologous hematopoietic stem cells is a well established therapeutic procedure. Despite advances in efficacy of the stem cell mobilization and apheresis process until now a predictive factor for the expected stem cell yield before initiation of mobilization therapy could not be identified. The main objective of our study was to evaluate alterations in enzymes involved in fatty acid metabolism on the level of gene expression in mononuclear cells, as changes in relative mRNA levels of these enzymes could represent the hematopoietic regenerative potential. Data of 23 consecutive patients with different lymphoid malignancies undergoing stem cell mobilization were analyzed. Our results show that mRNA levels of microsomal carnitine palmitoyltransferase in peripheral blood mononuclear cells quantified before application of mobilization therapy correlate positively with the amount of CD34 positive cells in peripheral blood before first apheresis, in the first apheresis product and in the total harvest outcome. The association of enzymes involved in fatty acid metabolism with hematoopoiesis was further confirmed in healthy subjects on altitude-adaptation training and in proliferating or differentiating HL60 cells. This gives evidence for a possible predictive value of such analyzes though further data of a larger sample are to be collected to confirm our observations.
Assuntos
Remoção de Componentes Sanguíneos , Carnitina O-Palmitoiltransferase/genética , Células-Tronco Hematopoéticas/citologia , RNA Mensageiro/sangue , Adolescente , Adulto , Altitude , Antígenos CD34/sangue , Ensaio de Unidades Formadoras de Colônias , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/análise , Proteínas de Ligação ao GTP/análise , Células HL-60 , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/patologia , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Proteínas Heterotriméricas de Ligação ao GTP/análise , Humanos , Leucócitos Mononucleares/enzimologia , Microssomos/enzimologia , Pessoa de Meia-Idade , Proteínas de Transporte de Cátions Orgânicos/análise , Transplante de Células-Tronco de Sangue Periférico , RNA Mensageiro/genética , Membro 5 da Família 22 de Carreadores de Soluto , Transplante AutólogoRESUMO
The aim of this study was to investigate the expression of osteocalcin (OCN) splicing variants in hematological malignancies. We analysed bone marrow obtained from two patients with chronic myeloid leukemia (CML), seven patients with other myeloproliferative diseases (MPD) and four patients with acute myeloid leukemia (AML). RT-PCR analyses were performed in order to assess and quantify spliced (OCNs) and unspliced (OCNu) mRNA, the associated transcription factors (AML1 and AML3) as well as c-KIT which is a marker for activated stem cells. Our data indicate that OCNs mRNA and OCN protein is expressed in c-KIT positive neoplastic stem cells in hematological malignancies.
