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Abstract
The homeobox gene Hoxb8 is activated in the murine myelomonocytic cell line WEHI-3B
as a result of intracisternal A particle integration. Cooperative activation between
Hoxa9 and Meis1 is induced by retroviral integration in BXH2 murine myeloid leukemias
and the myeloid leukemia cell line M1. The present study was conducted to examine
possible Meis gene activation and cooperative DNA binding of homeobox proteins in
WEHI-3B and to reveal the specific role of Hox and Meis genes in myeloid differentiation.
Northern blot analysis and reverse transcriptase polymerase chain reaction were performed
to examine homeobox genes expression. Electrophoretic mobility shift assay was performed
to evaluate DNA binding of homeobox proteins. Myeloid differentiation of 32Dcl3 was
induced by granulocyte colony-stimulating factor.
Meis2 was coactivated with Hoxb8 in WEHI-3B cells. DNA-protein complexes including
Hox, Meis, and Pbx were observed in WEHI-3B and 32Dcl3. Expression and the DNA-binding
complex of Hoxa9, Hoxb8, Meis1, and Meis2 were down-regulated during myeloid differentiation
of 32Dcl3 cells. Enforced expression of Hox or Meis genes inhibited myeloid differentiation
of 32Dcl3.
The results indicate that Meis2 is an important Meis gene for myeloid leukemogenesis
and that Hox and Meis are important genes for myeloid leukemogenesis through differentiation
block.