Oncogenic RAS genes impair erythroid differentiation of erythroleukaemia cells.
RAS mutations occur frequently in acute myeloid leukaemia and myelodysplasia, suggesting a functional role for this oncogene in leukaemogenesis. We show here, for the first time, that both N-RAS and H-RAS can impair erythroid differentiation of erythroleukaemia cells induced with hexamethylene bisacetamide. Transformation by RAS allowed extended proliferation in the presence of inducer and also inhibited maturation as measured by impaired haemoglobinization and reduction in cell size. These data provide an interesting counterpoint to the effect of mutant RAS on monocytic cells, where it has a potentiating effect on differentiation and may indicate a causal link between the activation of RAS and erythroid lineage dysplasia in preleukaemia.
Zaker
F
F
Department of Haematology, University of Wales College of Medicine, Cardiff, U.K.
Darley
R L
RL
al Sabah
A
A
Burnett
A K
AK
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D011905:Genes, ras; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D000081:Acetamides; D000970:Antineoplastic Agents; D006454:Hemoglobins; C014026:hexamethylene bisacetamide