TY - JOUR
T1 - In vivo gene amplification in non-cancerous cells
T2 - cholinesterase genes and oncogenes amplify in thrombocytopenia associated with lupus erythematosus
AU - Zakut, Haim
AU - Lapidot-Lifson, Yaron
AU - Beeri, Rachel
AU - Ballin, Ami
AU - Soreq, Hermona
PY - 1992/5
Y1 - 1992/5
N2 - The ACHE and BCHE genes, encoding the acetylcholine hydrolysing enzymes acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE), co-amplify with several oncogenes in leukemic patients with platelet deficiency (thrombocytopenia). This and other experiments implicated ACHE and BCHE in the development of bone marrow megakaryocytes, the progenitors of platelets. Therefore, we wished to find out whether cholinesterase gene amplification would also occur in non-cancerous platelet disorders and, if so, whether oncogenes would amplify in such cases as well. The autoimmune disease systemic lupus erythematosus (SLE) presents an appropriate model system for this issue, since patients with SLE may suffer from thrombocytopenia resistant to most treatment modalities. Here, we report a 40-80-fold amplification of genomic sequences from the ACHE and BCHE genes as well as the C-raf, V-sis and C-fes/fps oncogenes in peripheral blood cells from an SLE patient with severe thrombocytopenia. PvuII restriction analysis and DNA blot hybridization of the amplified ACHE and BCHE sequences demonstrated apparent aberrations in both genes, suggesting that malfunctioning of modified, partially amplified cholinesterase genes may be involved in the etiology of thrombocytopenia associated with SLE. These observations imply that cholinergic mechanisms regulate megakaryocytopoiesis, shed new light on the diverse hematologic findings characteristic of SLE, and may become valuable as diagnostic, treatment and prognostic tools in the follow-up of patients suffering from thrombocytopenia associated with SLE. Furthermore, these findings reinforce the notion that cholinesterase gene amplifications are causally related with platelet abnormalities in multiple hemopoietic disorders.
AB - The ACHE and BCHE genes, encoding the acetylcholine hydrolysing enzymes acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE), co-amplify with several oncogenes in leukemic patients with platelet deficiency (thrombocytopenia). This and other experiments implicated ACHE and BCHE in the development of bone marrow megakaryocytes, the progenitors of platelets. Therefore, we wished to find out whether cholinesterase gene amplification would also occur in non-cancerous platelet disorders and, if so, whether oncogenes would amplify in such cases as well. The autoimmune disease systemic lupus erythematosus (SLE) presents an appropriate model system for this issue, since patients with SLE may suffer from thrombocytopenia resistant to most treatment modalities. Here, we report a 40-80-fold amplification of genomic sequences from the ACHE and BCHE genes as well as the C-raf, V-sis and C-fes/fps oncogenes in peripheral blood cells from an SLE patient with severe thrombocytopenia. PvuII restriction analysis and DNA blot hybridization of the amplified ACHE and BCHE sequences demonstrated apparent aberrations in both genes, suggesting that malfunctioning of modified, partially amplified cholinesterase genes may be involved in the etiology of thrombocytopenia associated with SLE. These observations imply that cholinergic mechanisms regulate megakaryocytopoiesis, shed new light on the diverse hematologic findings characteristic of SLE, and may become valuable as diagnostic, treatment and prognostic tools in the follow-up of patients suffering from thrombocytopenia associated with SLE. Furthermore, these findings reinforce the notion that cholinesterase gene amplifications are causally related with platelet abnormalities in multiple hemopoietic disorders.
KW - Cholinesterase genes
KW - Hemopoietic development
KW - In vivo gene amplification
KW - Oncogenes
KW - Systemic lupus erythematosus
UR - http://www.scopus.com/inward/record.url?scp=13844307077&partnerID=8YFLogxK
U2 - 10.1016/0165-1110(92)90013-Y
DO - 10.1016/0165-1110(92)90013-Y
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C2 - 1374519
AN - SCOPUS:13844307077
SN - 0165-1110
VL - 276
SP - 275
EP - 284
JO - Mutation Research - Reviews in Genetic Toxicology
JF - Mutation Research - Reviews in Genetic Toxicology
IS - 3
ER -