Frequent co-expression of the HOXA9 and MEIS1 homeobox genes in human myeloid leukemias.
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.
Lawrence
H J
HJ
Division of Hematology and Medical Oncology, Department of Medicine, University of California VA Medical Center, San Francisco, CA, USA.
Rozenfeld
S
S
Cruz
C
C
Matsukuma
K
K
Kwong
A
A
Kömüves
L
L
Buchberg
A M
AM
Largman
C
C
D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007951:Leukemia, Myeloid / Q000235:genetics*; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; C097899:homeobox protein HOXA9