RESUMO
We recently reported that chronic myelogenous leukemia (CML) cells converted into myofibroblasts to create a microenvironment for proliferation of CML cells in vitro. To analyze a biological contribution of CML-derived myofibroblasts in vivo, we observed the characters of leukemic nonobese diabetes/severe combined immunodeficiency (NOD/SCID) mouse. Bone marrow nonadherent mononuclear cells as well as human CD45-positive cells obtained from CML patients were injected to the irradiated NOD/SCID mice. When the chimeric BCR-ABL transcript was demonstrated in blood, human CML cells were detected in NOD/SCID murine bone marrow. And CML-derived myofibroblasts composed with the bone marrow-stroma, which produced significant amounts of human vascular endothelial growth factor A. When the parental CML cells were cultured with myofibroblasts separated from CML cell-engrafted NOD/SCID murine bone marrow, CML cells proliferated significantly. These observations indicate that CML cells make an adequate microenvironment for their own proliferation in vivo.
RESUMO
The vascular endothelial growth factor (VEGF)-C system was analyzed in two cases of acute lymphocytic leukemia (ALL) with TCF3/PBX1 fusion to determine whether the VEGF-C system influences the growth of these ALL blasts. Bone marrow non-adherent mononuclear cells were prepared from the patients, and expressions of VEGFs and VEGF receptors (VEGFRs) were analyzed based on RNA and protein levels. Cell proliferation was also assayed with or without neutralizing antibodies to VEGFs. The patients' leukemic blasts expressed a significant amount of VEGF-C and VEGFR type-3. When anti-VEGF-C antibody was added to the blast cell cultures, cell proliferation was suppressed. These observations indicate that, in our ALL cases with TCF3/PBX1 fusion, VEGF-C autocrine stimulation plays an important role in the proliferation of ALL.
Assuntos
Cromossomos Humanos Par 19 , Cromossomos Humanos Par 1 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Fator C de Crescimento do Endotélio Vascular/análise , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/análise , Adulto , Anticorpos Monoclonais/farmacologia , Comunicação Autócrina , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Células da Medula Óssea/patologia , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Masculino , Fator de Transcrição 1 de Leucemia de Células Pré-B , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/análise , Fator C de Crescimento do Endotélio Vascular/genética , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Adulto JovemAssuntos
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 JovemAssuntos
Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Leucemia Promielocítica Aguda/patologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Adulto , Comunicação Autócrina/efeitos dos fármacos , Proliferação de Células , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Leucemia Promielocítica Aguda/metabolismo , Recidiva , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/fisiologiaRESUMO
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.