5-AMINOLEVULINATE SYNTHASE EXPRESSION AND HEMOGLOBIN-SYNTHESIS IN A HUMAN MYELOGENOUS LEUKEMIA-CELL LINE

We examined the effect of hemin, TGF-beta 1 and cytosine arabinoside ( Ara-C) on the levels of mRNAs for the erythroid-specific B-aminolevuli nate synthase (ALAS-E) and gamma-globin in various human myelogenous l eukemia cell lines, Detailed analyses were also made using one of them , YN-1, which was isolated and established in culture from a patient w ith chronic myelogenous leukemia, Our results demonstrate that gamma-g lobin protein level and the percentage of benzidine-positive cells in the cell line increased markedly (10- to 30-fold) upon treatment with hemin, TGF-beta 1, or Ara-C, In contrast, gamma-globin mRNA was alread y markedly expressed prior to treatment in 4 out of 9 cell lines exami ned, including YN-1, and the level increased only marginally after tre atment with hemin, ALAS-E mRNA levels were increased in YN-1 cells aft er treatment with TGF-beta 1 and Ara-C, while hemin treatment had litt le effect, These results indicate that heme supply is insufficient in YN-1 cells and suggest that hemin increases hemoglobin synthesis princ ipally at the post-transcriptional level, whereas TGF-beta 1 and Ara-C stimulate hemoglobin synthesis by activating efficient endogenous hem e supply in the cells.