EXPRESSION PATTERNS OF THE JEM-1 GENE IN NORMAL AND TUMOR-CELLS - UBIQUITY CONTRASTING WITH A FAINT, BUT RETINOID-INDUCED, MESSENGER-RNA EXPRESSION IN PROMYELOCYTIC NB4 CELLS

The JEM-1 gene, recently identified in acute promyelocytic leukemia (A PL) cells, codes for a novel nuclear factor (Duprez et al Oncogene 199 7; 14: 1563-1570). JEM-1 is kept silent in the APL cell line NB4, but up-regulated (3 kb transcript) during cell maturation. Here, we show t hat retinoic acid (RA)-induced JEM-1 expression is biphasic (peaks at 6 h and 48 h) and associated with the later stages of maturation. Reti noids, which cooperates with cAMP to induce maturation, also cooperate s with cAMP to up-regulate JEM-1, either in maturation-responsive NB4 cells or in NB4-R1 resistant subclones. APL patients showed a low, yet variable, level of JEM-1 mRNA in bone marrow. RA treatment induced an increase in the level of JEM-1 mRNA, as detected by a semi-quantitati ve PCR. This increase can result from both gene up-regulation or repla cement of leukemia cells by differentiated ones. Analysis of JEM-1 exp ression patterns in normal and tumor cells revealed that JEM-1 express ion was ubiquitous. Cell lines derived from monocytic and erythroid le ukemias, expressed low and high amounts of JEM-1 mRNA, respectively. U sing a JEM cDNA probe, distinct profiles of expression and different t ranscript sizes (4 kb, 3 kb and 2 kb) were also identified in tumour a nd normal non-hematopoietic tissues, while interestingly only the 3 kb transcript was up-regulated in NB4 cells. This work identifies JEM-1 as a novel ubiquitous gene whose expression is low in APL cells, but c an be restored by RA treatment, concomitant with cell maturation.