RESUMO
In this study, we describe an extremely rare case of co-existence of a Philadelphia chromosome positive acute megakaryoblastic and B-lymphoblastic mixed blast crisis of chronic myeloid leukemia with chronic lymphocytic leukemia. A morphological, immunophenotypical and cytogenetic study has been performed to characterize the case and in order to identify the origin of two disorders. After the failure of the conventional therapy, the patient was treated with Imatinib with a complete hematological and cytogenetic response and a marked reduction of bone marrow fibrosis.
Assuntos
Crise Blástica , Linfoma de Burkitt , Leucemia Linfocítica Crônica de Células B , Leucemia Megacarioblástica Aguda , Leucemia Mielogênica Crônica BCR-ABL Positiva , Neoplasias Primárias Múltiplas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas , Crise Blástica/genética , Crise Blástica/patologia , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Feminino , Humanos , Mesilato de Imatinib , Imunofenotipagem , Cariotipagem , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Megacarioblástica Aguda/genética , Leucemia Megacarioblástica Aguda/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Indução de RemissãoAssuntos
Fator 2 de Crescimento de Fibroblastos/biossíntese , Mieloma Múltiplo/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Células da Medula Óssea/metabolismo , Humanos , Glicoproteínas de Membrana/biossíntese , Pessoa de Meia-Idade , Proteoglicanas/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SindecanasAssuntos
Mieloma Múltiplo/patologia , Neoplasias Pleurais/secundário , Neoplasias Testiculares/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Evolução Fatal , Humanos , Imunoglobulina A/análise , Imunoglobulina G/análise , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/imunologiaRESUMO
Patients with multiple myeloma (MM) have increased bone marrow (BM) angiogenesis; however, the proangiogenic properties of myeloma cells and the mechanisms of MM-induced angiogenesis are not completely clarified. The angiopoietin system has been identified as critical in the regulation of vessel formation. In this study we have demonstrated that myeloma cells express several proangiogenic factors, and, in particular, we found that angiopoietin-1 (Ang-1), but not its antagonist Ang-2, was expressed by several human myeloma cell lines (HMCLs) at the mRNA and the protein levels. In a transwell coculture system, we observed that myeloma cells up-regulated the Ang-1 receptor Tie2 in human BM endothelial cells. Moreover, in an experimental model of angiogenesis, the conditioned medium of HMCLs significantly stimulated vessel formation compared with control or vascular endothelial growth factor (VEGF) treatment. The presence of anti-Tie2 blocking antibody completely blunted the proangiogenic effect of XG-6. Finally, our in vitro results were supported by the in vivo finding of Ang-1, but not Ang-2, mRNA and protein expression in purified MM cells obtained from approximately 47% of patients and by high BM angiogenesis in patients with MM positive for Ang-1, suggesting that the angiopoietin system could be involved, at least in part, in MM-induced angiogenesis.
Assuntos
Indutores da Angiogênese/fisiologia , Glicoproteínas de Membrana/fisiologia , Mieloma Múltiplo/metabolismo , Proteínas de Neoplasias/fisiologia , Neovascularização Patológica/metabolismo , Proteínas Proto-Oncogênicas , Adulto , Indutores da Angiogênese/análise , Indutores da Angiogênese/biossíntese , Indutores da Angiogênese/genética , Angiopoietina-1 , Angiopoietina-2 , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Células da Medula Óssea/metabolismo , Técnicas de Cocultura , Meios de Cultivo Condicionados/farmacologia , Fatores de Crescimento Endotelial/farmacologia , Endotélio/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Leucemia Plasmocitária/metabolismo , Leucemia Plasmocitária/patologia , Linfocinas/farmacologia , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Mieloma Múltiplo/irrigação sanguínea , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Neovascularização Patológica/genética , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Receptor TIE-2 , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
The biologic mechanisms involved in the pathogenesis of multiple myeloma (MM) bone disease are not completely understood. Recent evidence suggests that T cells may regulate bone resorption through the cross-talk between the critical osteoclastogenetic factor, receptor activator of nuclear factor-kappaB ligand (RANKL), and interferon gamma (IFN-gamma) that strongly suppresses osteoclastogenesis. Using a coculture transwell system we found that human myeloma cell lines (HMCLs) increased the expression and secretion of RANKL in activated T lymphocytes and similarly purified MM cells stimulated RANKL production in autologous T lymphocytes. In addition, either anti-interleukin 6 (anti-IL-6) or anti-IL-7 antibody inhibited HMCL-induced RANKL overexpression. Consistently, we demonstrated that HMCLs and fresh MM cells express IL-7 mRNA and secrete IL-7 in the presence of IL-6 and that bone marrow (BM) IL-7 levels were significantly higher in patients with MM. Moreover, we found that the release of IFN-gamma by T lymphocytes was reduced in presence of both HMCLs and purified MM cells. Furthermore, in a stromal cell-free system, osteoclastogenesis was stimulated by conditioned medium of T cells cocultured with HMCLs and inhibited by recombinant human osteoprotegerin (OPG; 100 ng/mL to 1 microg/mL). Finally, RANKL mRNA was up-regulated in BM T lymphocytes of MM patients with severe osteolytic lesions, suggesting that T cells could be involved at least in part in MM-induced osteolysis through the RANKL overexpression.