RESUMEN
Peripheral blood mononuclear cells from seventeen patients with primary myelodysplastic syndromes (MDS) in advanced stage were enriched for blasts and tested for (1) karyotype, (2) genomic configuration and (3) expression of IL-3, GM-CSF, FMS and EGR-1 genes which are all located on the long arm of chromosome 5. The expression of the M-CSF gene, that has been recently reassigned to the short arm of chromosome 1 (lp), was also investigated. Aims of the study were to (1) assess the potential role of the expression of these genes in the maintenance and expansion of the neoplastic clones and (2) search for constitutional losses or rearrangements of one allele followed by a deletion of the second allele of the same genes in the leukemic cells. The latter issue was investigated by comparing, in 8 cases, constitutive DNA from skin fibroblasts with leukemic DNA. Eleven of the 17 patients had abnormal karyotypes. The M-CSF gene was expressed in 6 cases and the FMS and the EGR-1 genes were expressed in 2 of the latter cases. An autocrine mechanism of growth could be hypothesized only for the 2 patients whose cells expressed both the M-CSF and FMS genes. No germline changes or rearrangements were observed in any of the genes studied. Thus, deregulation of genes encoding for certain hemopoietic growth factors or receptors does not seem to represent a major mechanism of MDS progression.
Asunto(s)
Cromosomas Humanos Par 5 , Proteínas de Unión al ADN/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Proteínas Inmediatas-Precoces , Interleucina-3/genética , Factor Estimulante de Colonias de Macrófagos/genética , Síndromes Mielodisplásicos/genética , Receptor de Factor Estimulante de Colonias de Macrófagos/genética , Factores de Transcripción/genética , Anciano , Anciano de 80 o más Años , Alelos , Aberraciones Cromosómicas , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 5/ultraestructura , Proteínas de Unión al ADN/biosíntesis , Proteína 1 de la Respuesta de Crecimiento Precoz , Femenino , Fibroblastos/patología , Regulación de la Expresión Génica , Genes , Factor Estimulante de Colonias de Granulocitos y Macrófagos/biosíntesis , Humanos , Interleucina-3/biosíntesis , Cariotipificación , Factor Estimulante de Colonias de Macrófagos/biosíntesis , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Monocitos/patología , Síndromes Mielodisplásicos/patología , Hibridación de Ácido Nucleico , Receptor de Factor Estimulante de Colonias de Macrófagos/biosíntesis , Eliminación de Secuencia , Factores de Transcripción/biosíntesisRESUMEN
Phosphoglucomutase 1, an enzyme mapping on the short arms of chromosome 1, is constantly missing in the leukemic cell line K-562 in spite of the presence of three No. 1 chromosomes. In the present work, a subclone of the cell line, K-562 (S)P, is described, where the enzyme can be demonstrated, thus excluding a small deletion as the cause for the lack of expression of phosphoglucomutase 1. The relationship between the presence of the enzyme and the karyotype changes in this subclone is analyzed. Addition of several inducers to the standard K-562 line failed to elicit expression of the enzyme.
Asunto(s)
Leucemia/enzimología , Fosfoglucomutasa/análisis , Línea Celular , Aberraciones Cromosómicas , Humanos , Leucemia/genética , Fosfoglucomutasa/genéticaRESUMEN
Differentiation-dependent expression of enzyme loci was evaluated in two human leukemic cell lines, the pluripotent leukemia cell line K-562 and the promyelocytic-like cell line HL-60. Acetylcholinesterase, a marker of erythroid differentiation, was present in K-562 cells and absent in HL-60 cells. This difference between the two lines was apparently unrelated to dosage effect; other enzymes carried on trisomic chromosomes in K-562 cells did not show dosage effect. Acetylcholinesterase activity was higher in subclone K-562 (S), which shows higher expression of hemoglobin. Electrophoretic mobility of acetylcholinesterase from K-562 (S) was of fetal type.
Asunto(s)
Acetilcolinesterasa/genética , Leucemia Mieloide Aguda/enzimología , Acetilcolinesterasa/sangre , Línea Celular , Bandeo Cromosómico , Células Clonales , Femenino , Feto , Hemoglobinas/genética , Humanos , Cariotipificación , Leucemia Mieloide Aguda/genética , EmbarazoRESUMEN
Preparations from various sources (human urines, mouse placenta and pregnant uterus extract, and fibroblast conditioned medium) were examined comparatively with affinity chromatography on Sepharose-Concanavalin A for the presence of Colony Stimulating Factor (CSF). The preparations from all sources constantly revealed two protein peaks: the proteins of the first peak, without Concanavalin A affinity, contained CSF in the material from pregnant uterus and fibroblast conditioned medium, while human urine preparation was devoid of CSF: the inhibitor of CFUc growth, detected and titrated in this peak, probably does not explain the lack of CFUc growth. The proteins from the second peak, specifically eluted with alpha-methyl D-glucopyranoside revealed CSF in all the examined preparations.