CHARACTERIZATION OF THE MONOCYTE-SPECIFIC ESTERASE (MSE) GENE

Carboxylic esterases are widely distributed in hematopoietic cells. Mo nocytes express the esterase isoenzyme (termed 'monocyte-specific este rase', MSE) that can be inhibited by NaF in the alpha-naphthyl acetate cytochemical staining. We examined the expression of MSE in normal ce lls and primary and cultured leukemia-lymphoma cells. The MSE protein was demonstrated by isoelectric focusing (IEF); MSE mRNA expression wa s investigated by Northern blotting and reverse transcriptase-polymera se chain reaction (RT-PCR), The following samples were positive for MS E protein and Northern mRNA expression: 20/24 monocytic, 4/32 myeloid, and 1/20 erythroid-megakaryocytic leukemia cell lines, but none of th e 112 lymphoid leukemia or lymphoma cell lines; of the normal purified cell populations only the monocytes were positive whereas, T, B cells , and granulocytes were negative; of primary acute (myelo) monocytic l eukemia cells (CD14-positive, FAB M4/M5 morphology) 14/20 were Norther n mRNA and 11/14 IEF protein positive. RT-PCR revealed MSE expression in 29/49 Northern-negative lymphoid leukemia-lymphoma cell lines. The RT-PCR signals in monocytic cell lines were on average 50-fold stronge r than the mostly weak trace expression in lymphoid specimens. On trea tment with various biomodulators, only all-trans retinoic acid signifi cantly upregulated MSE message and protein levels but could not induce new MSE expression in several leukemia cell lines; lipopolysaccharide and interferon-gamma increased MSE expression in normal monocytes. An alysis of DNA methylation with sensitive restriction enzymes showed no apparent regulation of gene expression by differential methylation; t he MSE gene is evolutionarily conserved among mammalian species; the h alf-life of the human MSE transcripts was about 5-6 h. The extent of M SE expression varied greatly among different monocytic leukemia sample s. However, the MSE overexpression in a significant number of specimen s was not associated with gene amplification, gross structural rearran gements or point mutations within the cDNA region. Taken together, the results suggest that MSE expression is not absolutely specific for, b ut strongly associated with cells of the monocytic lineage; MSE is eit her not expressed at all or expressed at much lower levels in cells fr om other lineages. The biological significance, if any, of rare MSE me ssages in lymphoid cells detectable only by the hypersensitive RT-PCR remains unclear. Further studies on the regulation of this gene and on the physiological function of the enzyme will no doubt be informative with respect to its striking overexpression in some malignant cells a nd to a possible role in the pathobiology of monocytic leukemias.