Undeerstanding the key events occurring during the reprogramming of erythroleukemia cells; larger-scle gene expression profiling during murine erythroleukemia cell differentiation using cENA microarray

초록

MEL cells are transformed erythroid precursors that are blocked at about the proerythroblast stage of differentiation. Treatment of cells with agents, like HMBA, causes them to reinitiate erythroid terminal differentiation culminating in accumulation of erythrocyte-specific markers, cell-cycle arrest, and loss of tumorigenicity. MEL cells also provide an opportunity to study the changes occurring during reprogramming of tumor cells into their normal differentiation program. Although a great deal has been learned about the factors controlling gene expression during differentiation of MEL cells, much less is known about the mechanisms that determine the commitment of differentiation and maintain fully mature cells in the state of permanent cell cycle withdrawal. As an effort to uncover the cellular and molecular mechanisms of erythropoietic differentiation, we have compared gene expression profiles between uncommitted and differentiating MEL cells using cDNA microarray and identified a set of genes that preferentially expressed in uncommitted or differentiating cells. During HMBA-induced differentiation, changes in signal transduction-, transcription-, cell metabolism- and extracellular matrix-related genes were dominated over preferentially expressed genes and some of them were correlated with the published data. This kind of study may provide fundamental clues for the understanding of erythropoiesis as well as for leukemia therapy.