Assuntos
Neoplasias do Sistema Nervoso Central/enzimologia , Neoplasias do Sistema Nervoso Central/genética , Leucemia Promielocítica Aguda/enzimologia , Leucemia Promielocítica Aguda/genética , Mutação , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Feminino , Duplicação Gênica , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Sequências de Repetição em Tandem , Adulto JovemRESUMO
To elucidate the biological characteristics of chronic myelogenous leukemia (CML) cells, we observed morphological and functional changes of CML cells during primary long-term culture, in which their morphology changed to that of myofibroblasts with similar molecular characteristics to the parental CML cells including BCR-ABL fusion gene, and produced cytokines such as granulocyte colony-stimulating factor, interleukin-6, and vascular endothelial growth factor (VEGF)-A. When cultured on the CML-derived myofibroblasts, parental non-adherent CML cells significantly proliferated. When anti-VEGF-A-neutralizing antibody was added to the cultures, non-adherent CML cell proliferation was significantly inhibited. These observations indicate that CML cells can convert their morphology and function to adherent myofibroblasts, and produce a significant amount of cytokine to give a growth-promotion activity to CML cells.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Miofibroblastos/patologia , Microambiente Tumoral/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/farmacologia , Adulto , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Adesão Celular/fisiologia , Separação Celular , Transdiferenciação Celular/efeitos dos fármacos , Transdiferenciação Celular/genética , Transdiferenciação Celular/fisiologia , Células Cultivadas , Análise Citogenética , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/fisiologia , Genes abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Miofibroblastos/metabolismo , Miofibroblastos/fisiologia , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/fisiologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The availability of highly active anti-retroviral therapy (HAART) has greatly improved the outcome of human immunodeficiency virus type-1 (HIV-1) infection and disease. We report here on a case of an HIV-1-seropositive patient with acute myelogenous leukemia who underwent a successful allogeneic unrelated bone marrow transplantation following HAART. A 40-year-old Japanese HIV-seropositive man underwent allogeneic unrelated bone marrow transplantation using a myeloablative pretransplant-conditioning regimen. Neutrophil engraftment occurred on day +18, and donor chimerism was achieved on day +27. During pre- and post- transplantation, the HAART was not interrupted. Over 1 year after transplantation, the patient is alive and in continuous complete remission with undetectable levels of HIV-1 RNA. HAART can lead to a successful hematopoietic stem cell transplantation without severe opportunistic infections.
Assuntos
Terapia Antirretroviral de Alta Atividade , Transplante de Medula Óssea , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Leucemia Mieloide Aguda/terapia , Adulto , Infecções por HIV/complicações , HIV-1/genética , Humanos , Leucemia Mieloide Aguda/complicações , Masculino , RNA Viral , Indução de RemissãoRESUMO
Bone marrow-myofibroblasts, a major component of bone marrow-stroma, are reported to originate from hematopoietic stem cells. We show in this paper that non-adherent leukemia blasts can change into myofibroblasts. When myeloblasts from two cases of acute myelogenous leukemia with a fusion product comprising mixed lineage leukemia and RNA polymerase II elongation factor, were cultured long term, their morphology changed to that of myofibroblasts with similar molecular characteristics to the parental myeloblasts. The original leukemia blasts, when cultured on the leukemia blast-derived myofibroblasts, grew extensively. Leukemia blasts can create their own microenvironment for proliferation.