Erythroleukemia differentiation: Distinctive responses of the erythroid-specific and the nonspecific δ-aminolevulinate synthase mRNA

We have examined the levels of δ-aminolevulinate synthase (ALAS) mRNAs encoding the erythroid-specific (ALAS-E) and the nonspecific (ALAS-N) ALAS isozymes in murine Friend virus-transformed erythroleukemia (MEL) cells. Both ALAS-E and ALAS-N mRNAs were detected in a clone of dimethyl sulfoxide (Me₂SO)-sensitive MEL cells, termed DS-19, without cross-hybridization. Untreated DS-19 cells contained ~10-fold more ALAS-E mRNA than ALAS-N mRNA. When DS-19 cells were treated with Me₂SO or hemin, ALAS-N mRNA declined rapidly, which was followed by a marked increase in ALAS-E mRNA. Similarly, the immunoquantifiable ALAS-N protein decreased, while the ALAS-E protein increased upon Me₂SO treatment. A clone of Me₂SO-resistant cells, termed DR-1, which fails to undergo erythroid differentiation, was found to lack ALAS-E mRNA, whereas it showed significant induction responses of mRNAs for other heme pathway enzymes by Me₂SO treatment. DR-1 cells contained a similar level of an erythroid-specific transcription factor, GATA-1, as did DS-19 cells, and had neither major deletion nor rearrangement of the ALAS-E gene. These findings indicate that the genes encoding the two ALAS isozymes are under separate controls and suggest that ALAS-E mRNA accumulation is responsible for increased heme synthesis in MEL cells undergoing erythroid differentiation.