Cloning and chromosomal localization of the gene encoding human cyclin D-binding Myb-like protein (hDMP1)

The murine transcription factor murine cyclin D-binding Myb-like protein (m Dmp1) arrests the cell cycle in G(1) phase, through an activity that can be overridden by direct interaction with the D-type cyclins. Here, we describ e the identification, sequence, chromosomal localization, and expression of the human cognate, hDMP1. The hDMP1 cDNA contains a 2280 bp open reading f rame that shares a high degree of identity with the mDmp1 coding region. Th e 4.4 kb hDMP1 messenger RNA is ubiquitously expressed in normal human tiss ues, with highest levels in testis and substructures within the brain. By u se of fluorescence in situ hybridization with a human genomic P1 probe, we assigned hDMP1 to chromosome 7, band q21. This chromosomal region is freque ntly deleted as part of the 7q-minus and monosomy 7 abnormalities of human acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We analyze d hDMP1 copy number by fluorescence in situ hybridization in leukemic blast s from nine patients with abnormalities of the long arm of chromosome 7, an d in each case one allele of the hDMP1 gene was deleted. Functional analysi s of the mDmp1 protein has shown that it negatively regulates cell prolifer ation, which suggests that this gene is a candidate suppressor of malignant transformation. Further study will be needed to determine whether gene-spe cific mutations implicate hDMP1 as a tumor suppressor in acute leukemias wi th deletions of the long arm of chromosome 7 or in other types of human mal ignancy. (C) 1998 Published by Elsevier Science B.V. All rights reserved.