Preferential expression of HMGI-C isoforms lacking the acidic carboxy terminal in human leukemia

The high mobility group HMGI chromosomal proteins are an important component of chromatin. The HMGI-C protein consists of three amino terminal DNA binding domains ('AT hooks'), a linker region and an acidic carboxy domain. In mesenchymal tumors, chromosomal translocations of 12q13-15 result in fusion proteins containing the AT hooks and novel carboxy terminals. We have investigated the status of the HMGI-C gene in two cases of leukemia with anomalies of chromosome 12q and identified three novel isoforms (designated α, β and γ) derived from alternate splicing. One of the patients expressed all three isoforms, whereas the second patient expressed only the γ isoform; preferential expression of the HMGI-Cγ isoform was also detected in the leukemic cell lines ML3 and BV173. The results are consistent with a crucial role for truncation of the acidic carboxy domain of HMGI-C in abnormal growth.