Key regulatory gene expression in erythroleukemia differentiation

ABSTRACT

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