key regulatory gene expression in erythroleukemia differentiation

the characteristics of cellular and molecular mechanisms associated with cell proliferation and differentiation is important to understand malignancy. in this report we characterise a leukemic model, d5a1, to study the action of differentiation agent, cellular events and gene expression of the selected transcription factors. cells induced with 4 mm hexamethylene bisacetamide (hmba) caused signs of erythroid differentiation (changes in morphology and size, haemoglobinisation) and cessation of proliferation including accumulation of cells in g0/g1. treatment with hmba caused a time-related decrease of tumorigenicity detectable by 48 hour. northern-blotting showed induction of -amino levulinic acid synthase-erythroid (alas-e) mrna at 48 hours and appeared in a strong level subsequently. c-myc (myelocytomatosis) and c-myb (myeloblastoma) mrna levels decreased transiently in early hours returning to control values by 24 hour and decreased again. stem cell leukaemia (scl) and gata-1 mrna were markedly down regulated in early hours and then returned back. a later time point, upregulation of gata-1 and scl was relevant to maturation phenotype. these data provide a useful model to study the cellular and molecular events in leukomogenesis and action of differentiation therapy in leukaemia