PMID:15556871

Citation	Ernst, P, Mabon, M, Davidson, AJ, Zon, LI and Korsmeyer, SJ (2004) An Mll-dependent Hox program drives hematopoietic progenitor expansion. Curr. Biol. 14:2063-9
Abstract	Chromosomal translocations disrupting the Mixed lineage leukemia (Mll) gene result in leukemia, with aberrant expression of some native Mll target genes (reviewed in). The Mll gene encodes a Trithorax-group chromatin regulator that is essential for the development of hematopoietic stem cells (HSCs) during embryogenesis. Like Trithorax, MLL positively regulates clustered homeodomain or Hox genes, yet the role of Hox genes collectively in the development of the mammalian hematopoietic system has been difficult to ascertain because of redundancy among Hox paralogs. Here, we show that in the absence of MLL, early hematopoietic progenitors develop despite reduced expression of HoxA, HoxB, and HoxC genes. However, these progenitors exhibit a marked reduction in their ability to generate hematopoietic colonies, a subsequent process requiring cell division and differentiation. Reactivation of a subset of Hox genes or, remarkably, reexpression of a single Hox gene in Mll-deficient progenitors rescued hematopoietic-colony frequency and growth. In contrast, expression of other MLL target genes such as Pitx2 or expression of anti-apoptotic BCL-2 failed to rescue hematopoietic-colony frequency. Furthermore, our results highlight a shared function of Hox proteins at this point in the development of the hematopoietic system.
Links	PubMed Online version:10.1016/j.cub.2004.11.012
Keywords	Cells, Cultured; DNA-Binding Proteins/metabolism; Embryo, Mammalian/cytology; Flow Cytometry; Gene Expression Regulation, Developmental; Gene Transfer Techniques; Genes, Homeobox/genetics; Hematopoiesis/genetics; Hematopoiesis/physiology; Hematopoietic Stem Cells/metabolism; Humans; Myeloid-Lymphoid Leukemia Protein; Proto-Oncogenes; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:KMT2A		GO:0060216: definitive hemopoiesis	ECO:0000315:		P		Figure 2C shows the failure of MII-deficient cells to give rise to hematopoietic colonies. Figure 2 A and B shows the normal development of cells for MII and MII-deficient cells, indicating normal differentiation. Thus, MII-deficient cells develop normally until hematopoietic differentiation. The lack of differentiation results in a failure to develop a hematopoietic center in the body.	complete CACAO 4421
MOUSE:KMT2A	involved_in	GO:0060216: definitive hemopoiesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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