Lineage-specific function of Engrailed-2 in the progression of chronic myelogenous leukemia to T cell blast crisis

Deregulations in transcription factors lead to abnormal development, like in leukaemias, where chromosomal abnormalities either create chimeric TFs or alter the expression of the existing ones. The characterization of the precise functions of the TFs that regulate blood formation is essential to understand how these mechanisms are altered in malignancies. We have found that Engrailed-2 becomes methylated in the progression to blast crises of T-cell phenotype in chronic myelogenous leukaemia (CML) in human samples. Subsequently we found that En2 is expressed during T-cell development in the mouse and in humans. Engrailed-2 plays an essential role in central nervous system development but it has not been shown to participate in haematopoiesis. Many TFs have been found to play essential functions both in nervous system and blood development, thus making En2 a likely candidate to be involved in haematopoiesis. We have studied haematopoiesis of wild-type vs. En2 knockout mice. To increase our understanding of the possible molecular role(s) of En2 during T cell development, we have compared by microarray analysis the gene expression patterns of En2-/- versus WT sorted DP thymocytes and also CD8+ splenocytes (the two populations in which we had detected En2 expression).

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