Differential epigenetic regulation between the alternative promoters, PRDM1α and PRDM1ß, of the tumour suppressor gene PRDM1 in human multiple myeloma cells.

Multiple myeloma (MM) is a B-cell neoplasm that is characterized by the accumulation of malignant plasma cells in the bone marrow. The transcription factor PRDM1 is a master regulator of plasma cell development and is considered to be an oncosuppressor in several lymphoid neoplasms. The PRDM1ß isoform is an alternative promoter of the PRDM1 gene that may interfere with the normal role of the PRDM1α isoform. To explain the induction of the PRDM1ß isoform in MM and to offer potential therapeutic strategies to modulate its expression, we characterized the cis regulatory elements and epigenetic status of its promoter. We observed unexpected patterns of hypermethylation and hypomethylation at the PRDM1α and PRDM1ß promoters, respectively, and prominent H3K4me1 and H3K9me2 enrichment at the PRDM1ß promoter in non-expressing cell lines compared to PRDM1ß-expressing cell lines. After treatment with drugs that inhibit DNA methylation, we were able to modify the activity of the PRDM1ß promoter but not that of the PRDM1α promoter. Epigenetic drugs may offer the ability to control the expression of the PRDM1α/PRDM1ß promoters as components of novel therapeutic approaches.

Maternal and fetal serum transformed alpha-fetoprotein levels in normal pregnancy.

AIM: To evaluate transformed alpha-fetoprotein (t-AFP) (a new molecular conformation of alpha-fetoprotein) levels in maternal serum and fetal serum in normal pregnancy. METHODS: Prospective longitudinal study. Fifty pregnant women were studied in two groups: 25 were evaluated in each trimester of pregnancy and near term (12, 20, 32 and 36 weeks) and the other 25 were evaluated at the time of planned cesarean section at term. In the first group, maternal serum t-AFP was measured and in the second group, maternal and fetal serum t-AFP were analyzed. RESULTS: Maternal serum t-AFP levels (medians) were 14.73 ng/mL in the first trimester, 28.29 ng/mL in the second trimester, 30.45 ng/mL in the early third trimester and 8.06 ng/mL in late pregnancy. t-AFP levels were significantly higher in maternal than in fetal serum (P < 0.001). There were no significant correlations between AFP and t-AFP levels in maternal versus fetal serum. CONCLUSIONS: t-AFP increases during pregnancy until the early third trimester and then falls before delivery. t-AFP levels are higher in maternal than in fetal serum which suggests that native AFP is transformed to t-AFP either in the mother or in the placenta.