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