Frequent co-expression of the HOXA9 and MEIS1 homeobox genes in human myeloid leukemias

H. J. Lawrence, S. Rozenfeld, C. Cruz, Karen Matsukuma, A. Kwong, L. Kömüves, A. M. Buchberg, C. Largman

Research output: Contribution to journalArticle

177 Scopus citations

Abstract

There is increasing evidence that HOX homeobox genes play a role in leukemogenesis. Recent studies have demonstrated that enforced co-expression of HOXA9 and MEIS1 in murine marrow leads to rapid development of myeloid leukemia, and that these proteins exhibit cooperative DNA binding. However, it is unclear whether co-activation of HOXA9 and MEIS genes is a common occurrence in human leukemias. We surveyed expression of HOXA9 and MEIS1 in 24 leukemic cell lines and 80 patient samples, using RNase protection analyses and immunohistochemistry. We demonstrate that the expression of HOXA9 and MEIS1 in leukemia cells is uniquely myeloid, and that these genes are commonly co-expressed in myeloid cell lines and in samples of acute myelogenous leukemia (AML) of all subtypes except in promyelocytic leukemia. While HOXA9 is expressed in most cases of chronic myelogenous leukemia, MEIS1 is weakly expressed or not at all. Immunohistochemical staining of selected AML samples showed moderate to high levels of HOXA9 protein, primarily cytoplasmic, in leukemic myeloblasts, with weaker and primarily nuclear staining for MEIS1. These data support the concept that co-activation of HOXA9 and MEIS1 is a common event in AML, and may represent a common pathway of many different oncogenic mutations.

Original languageEnglish (US)
Pages (from-to)1993-1999
Number of pages7
JournalLeukemia
Volume13
Issue number12
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Keywords

  • Homeobox genes
  • Myeloid leukemia
  • Oncogenes
  • Transcription factors

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Frequent co-expression of the HOXA9 and MEIS1 homeobox genes in human myeloid leukemias'. Together they form a unique fingerprint.

  • Cite this

    Lawrence, H. J., Rozenfeld, S., Cruz, C., Matsukuma, K., Kwong, A., Kömüves, L., Buchberg, A. M., & Largman, C. (1999). Frequent co-expression of the HOXA9 and MEIS1 homeobox genes in human myeloid leukemias. Leukemia, 13(12), 1993-1999. https://doi.org/10.1038/sj.leu.2401578