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December 1999, Volume 13, Number 12, Pages 1993-1999
Table of contents    Previous  Abstract  Next   Article  PDF
Original manuscript
Frequent co-expression of the HOXA9 and MEIS1 homeobox genes in human myeloid leukemias
H J Lawrence1, S Rozenfeld1, C Cruz1, K Matsukuma1, A Kwong1, L Kömüves1, A M Buchberg2 and C Largman1

1Division of Hematology and Medical Oncology, Department of Medicine, University of California VA Medical Center, San Francisco, CA, USA

2Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA, USA

Correspondence to: H J Lawrence, 1, rue Laurent Fries, BP 163, 67 404 Illkirch Codex, France

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.

Keywords

homeobox genes; myeloid leukemia; oncogenes; transcription factors

Received 8 October 1998; accepted 26 July 1999
December 1999, Volume 13, Number 12, Pages 1993-1999
Table of contents    Previous  Abstract  Next   Article  PDF