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 leukemo genesis. Recent studies have demonstrated that enforced co-expression of HO XA9 and MEIS1 in murine marrow leads to rapid development of myeloid leukem ia, and that these proteins exhibit cooperative DNA binding. However, it is unclear whether co-activation of HOXA9 and MEIS genes is a common occurren ce in human leukemias. We surveyed expression of HOXA9 and MEIS1 in 24 leuk emic cell lines and 80 patient samples, using RNase protection analyses and immunohistochemistry. We demonstrate that the expression of HOXA9 and MEIS 1 in leukemia cells is uniquely myeloid, and that these genes are commonly co-expressed in myeloid cell lines and in samples of acute myelogenous leuk emia (AML) of all subtypes except in promyelocytic leukemia. While HOXA9 is expressed in most cases of chronic myelogenous leukemia, MEIS1 is weakly e xpressed or not at all. Immunohistochemical staining of selected AML sample s showed moderate to high levels of HOXA9 protein, primarily cytoplasmic, i n leukemic myeloblasts, with weaker and primarily nuclear staining for MEIS 1. 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.