Inhibition of myeloid differentiation by Hoxa9, Hoxb8, and Meis homeobox genes

Takashi Fujino, Yukari Yamazaki, David A. Largaespada, Nancy A. Jenkins, Neal G. Copeland, Katsuiku Hirokawa, Takuro Nakamura

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Objective. 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. Materials and Methods. 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. Results. 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. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)856-863
Number of pages8
JournalExperimental Hematology
Volume29
Issue number7
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
This work was supported in part by Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Priority Areas (C) from the Ministry of Education, Science, Sports and Culture, and by the National Cancer Institute, DHHS. We thank Ryoko Iwata and Mizuko Ohsaka for technical assistance.

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