Coamplification of human acetylcholinesterase and butyrylcholinesterase genes in blood cells: correlation with various leukemias and abnormal megakaryocytopoiesis.

Abstract

To study the yet unknown role of the ubiquitous family of cholinesterases (ChoEases) in developing blood cells, the recently isolated cDNAs encoding human acetyicholinesterase (AcChoEase; acetylcholine acetyihydrolase, EC 3.1.1.7) and butyrylcholinesterase (BtChoEase; cholinesterase; acylcholine acylhydrolase, EC 3.1.1.8) were used in blot hybridization with peripheral blood DNA from various leukemic patients. Hybridization signals (10-to 200-fold intensifled) and modified restriction patterns were observed with both cDNA probes in 4 of the 16 leukemia DNA preparations examined. These reflected the amplification of the corresponding AcChoEase and BtChoEase genes (ACHE and CHE) and alteration in their structure. Parallel analysis of 30 control samples revealed nonpolymorphic, much weaker hybridization signals for each of the probes. In view of previous reports on the effect of acetylcholine analogs and ChoEase inhibitors in the induction of megakaryocytopoiesis and production of platelets in the mouse, we further searched for such phenomena in nonleukemic patients with platelet production disorders. Amplifications of both ACHE and CHE genes were found in 2 of the 4 patients so far examined. Pronounced coamplification of these two related but distinct genes in correlation with pathological production of blood cells suggests a functional role for members of the ChoEase family in megakaryocytopoiesis and raises the question whether the coamplification of these genes could be causally involved in the etiology of hemocytopoietic disorders.

Murine and human mast cell express acetylcholinesterase

“…By the use of specific inhibitors we demonstrated that some of the cholinesterase activity was probably due to BuChE activity, and some of it due to AChE activty. The coexpression of the two cholinestreases in one cell type is not surprising, since in other ceils of the hematopoietic system there is also coexpression of both enzyme types [20]. The detected AChE activity level was similar to that reported for leukocytes [21].…”

Acetylcholinesterase and butyrylcholinesterase genes coamplify in primary ovarian carcinomas.

“…Further analysis revealed the occurrence of coamplified ACHEDNA and CHEDNA sequences in genomic DNA from peripheral blood cells of leukemic patients (9). Altogether, these findings raised the question whether the previously reported high level of expression of the ACHE and CHE enzymes in tumors (10, 1 1) is effected by gene amplification.…”

Cholinesterase activity as biomarker of neurotoxicity: utility in the assessment of aquatic environment contamination

“…In embryonic life, definition of the role of cholinesterases in cellular proliferation and differentiation have started the investigations on possible involvement of BChE and AChE in tumorogenesis. Abnormal expression of both BChE and AChE, and in vivo amplification of their genes have been observed in intracranial neoplasms such as meningioma (67), glioma (68), and acuostic neurinomas (69), lung cancers (70), megakaryocytopoietic disorders and leukemias (71), ovarian tumors (72). It is also shown that AChE and BChE modulate cell adhesion in human neuroblastoma cells (62).…”

“…It is also shown that AChE and BChE modulate cell adhesion in human neuroblastoma cells (62). Antisense blocking of BChE has been shown to result in an inhibition of megakaryocytopoiesis and application of similar techniques in embryonic chick retinal cell resulted in an inhibition of proliferation (61,71). So we will read more about the relationship between BChE and tumorogenesis and the usage of specific BChE inhibitors used as chemothreapeutic agents in the future also.…”