C EBP-EPSILON - CHROMOSOMAL MAPPING AND MUTATIONAL ANALYSIS OF THE GENE IN LEUKEMIA AND PRELEUKEMIA/

We and others have cloned a novel human gene CCAAT/enhancer-binding pr otein epsilon (C/EBP-epsilon) encoding a member of the C/EBP gene fami ly. It is exclusively expressed in myeloid and T-lymphoid cells and ap pears to have an important role in inducing expression of several myel oid-specific genes. We used a polymerase chain reaction (PCR)-based te chnique to examine DNA from 93 hamster/human radiation hybrid clones i n order chromosomally to map C/EBP-epsilon to 14q11.2 (between D14S264 and D14S275) which is telomeric to the T-cell receptor alpha and delt a genes and centromeric to several other myeloid gene products includi ng Cathepsin G (CTSG) and Chymase-1 (CMA1). To determine whether C/EBP -epsilon behaves as an altered tumor-suppressor gene, samples from pat ients with acute myelogenous leukemia (AML) and myelodysplastic syndro me (MDS) evolving to AML were studied for loss of heterozygosity (LOH) using microsatellite sequences that we identified within 0.2 kb of th e amino-terminus of the human C/EBP-epsilon gene. Allelic loss of the C/EBP-epsilon gene was detected in four out of 20 (20%) evolving MDS c ases and in none of the 17 AML and 17 T-cell leukemia cases. Mutationa l analysis of the gene was performed using PCR-SSCP on 37 AML and 40 M DS cases including those with LOH at the gene. No abnormalities were f ound suggesting that the altered gene in this region is not C/EBP-epsi lon. Also, C/EBP-epsilon was examined by Southern blot analysis on DNA samples from 20 AML patients and 10 AML cell lines. No rearrangements or amplifications of the gene were detected. Taken together, we have mapped C/EBP-epsilon to 14q11.2, a region containing other myeloid and T-lymphoid specific genes. Furthermore, no structural alterations wer e detected in the C/EBP-epsilon gene. (C) 1997 Elsevier Science Ltd.