RESUMO
The expression of retinoic acid nuclear receptor gene RARα and its relationship with expression of APE1, YB-1, and MDR1 genes was studied in bone marrow aspiration biopsy specimens from 22 patients with newly detected multiple myeloma. The expression of RARα directly correlated with the expression of APE1/YB-1/MDR1 pattern genes. Groups differing by expression of RARα exhibited significant differences in the overall survival of patients; concordant and simultaneous changes in the expression of all genes of the APE1/YB-1/MDR1 pattern suggested the level of RARα gene expression as a potential prognostic factor in the pathogenesis of multiple myeloma.
Assuntos
DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Mieloma Múltiplo/metabolismo , Receptor alfa de Ácido Retinoico/genética , Proteína 1 de Ligação a Y-Box/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Prognóstico , Receptor alfa de Ácido Retinoico/metabolismo , Proteína 1 de Ligação a Y-Box/metabolismoRESUMO
The significance of quantitative changes of ALDH1A1 and RDH10 gene expression in 22 non-treated multiple myeloma patients were studied. We found a direct correlation between the expression of ALDH1A1 and RDH10 genes. We showed that ALDHA1 and RDH10 expression were inversely related with expression of a key gene for all-trans-retinoic acid catabolism, CYP26A1, and correlated with expression of RARα and PPARß/ genes. In addition for the first time it was re- vealed that increased expression of ALDH1A1-RDH10-RARα- PPARß/δ pattern could be considered as adverse prognostic factor associated with a higher concentration of paraprotein and worst overall survival of patients with newly diagnosed multiple myeloma.
Assuntos
Oxirredutases do Álcool/biossíntese , Aldeído Desidrogenase/biossíntese , Regulação Neoplásica da Expressão Gênica , Mieloma Múltiplo , Proteínas de Neoplasias/biossíntese , PPAR delta/biossíntese , PPAR beta/biossíntese , Receptor alfa de Ácido Retinoico/biossíntese , Tretinoína/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Oxirredutases do Álcool/genética , Aldeído Desidrogenase/genética , Família Aldeído Desidrogenase 1 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Proteínas de Neoplasias/genética , PPAR delta/genética , PPAR beta/genética , Retinal Desidrogenase , Receptor alfa de Ácido Retinoico/genéticaRESUMO
Insulin effects of human multiple myeloma cell survival were studied on RPMI1640, RPMI8226, and IM9 lines differing by differentiation degree. The effects of exogenous insulin on tumor cell growth and survival varied. Insulin alone did not improve the viability of myeloma cells, while in combination with serum growth factors increased it. The IM9 cells with immunophenotype (CD(138+), CD(38-), CD(45+), CD(56-), CD(19+)) exhibited the highest sensitivity to serum growth factors, while RPMI1640 and RPMI8226 cells with (CD(138+), CD(38+), CD(45-), CD(56±), CD(19-)) immunophenotype were less sensitive. Studies of gene expression showed a significantly lower level of IRA mRNA expression in IM9 vs. RPMI1640 and RPMI8226 cells.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Insulina/farmacologia , Mieloma Múltiplo/fisiopatologia , Linhagem Celular Tumoral , Primers do DNA/genética , Eletroforese em Gel de Ágar , Humanos , Imunofenotipagem , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sais de Tetrazólio , TiazóisRESUMO
Coexpression of two mRNA isoforms for insulin-like growth factor-1 (IGF-1A and IGF-1B) and expression of YB-1 mRNA were analyzed in the bone marrow aspirates from 19 patients with multiple myeloma. It was shown that mRNA isoforms for IGF-1A and IGF-1B were mainly expressed in samples with hyperexpression of YB-1 mRNA, and, on the contrary, practically were not expressed (except sporadic cases) in samples with low level of YB-1 mRNA expression. Coexpression of mRNA isoforms for IGF-1A and IGF-1B were observed in 80% patients with multiple myeloma.
