Gene required for formation of blood cells

Scientists have identified a gene that is required for formation of all types of blood cells during embryonic development. The research enhances our understanding of the genetic pathways that are critical for normal blood cell generation. The results of this study are also likely to provide clues about the genes that play a central role in diseases characterized by pathological overproduction of abnormal blood cells, such as human leukemias.

A gene called Mixed-Lineage Leukemia (MLL) gene is mutated in some forms of human leukemia and is thought to play a role in blood cell development. MLL regulates a special set of genes known as HOX genes that are important for embryonic development of the body. Dr. Stanley Korsmeyer and colleagues from Dana-Farber Cancer Institute were interested in determining exactly what role MLL plays in the development of blood cells, a complex process known as hematopoiesis. In studies using adult and fetal genetically engineered animals, the researchers discovered that without MLL, normal production of blood cells did not occur. In fact, MLL was absolutely required for the development of the earliest type of fetal blood cell, called a hematopoietic stem cell, which gives rise to all forms of mature blood cells.

The researchers suggest that the dramatic effects of MLL on blood cell formation may be mediated via MLL control of a critical complement of genes that are necessary for different aspects of hematopoiesis. "To date, no individual or compound HOX gene knockout recapitulates the block in definitive hematopoiesis observed in MLL mutants, suggesting that the MLL-dependent hematopoietic program will prove to be a broader set of target genes, or a specific subset of HOX genes," writes Dr. Korsmeyer.

P. Ernst, J.K. Fisher, W. Avery, S. Wade, D. Foy, and S.J. Korsmeyer: "Definitive Hematopoiesis Requires the Mixed-Lineage Leukemia Gene"

Published in Developmental Cell, Volume 6, Number 3, March 2004, pages 437-444.

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