title: Disturbed expression of the anti-apoptosis gene, survivin, and EPR-1 in hematological malignancies.
abstract: Survivin is a newly discovered inhibitor of the apoptosis protein, IAP, expressed during development and in human cancers. The effector cell protease receptor-1 (EPR-1) gene is oriented in the opposite direction on the same DNA double strand. Thus, the Survivin and EPR-1 (Survivin/EPR-1) genes exist in a head-to-head configuration. It is not clear whether mutual expression of the Survivin/EPR-1 genes occurs in both normal cells and cancer cells. Here, we investigated the mutual expression of the Survivin/EPR-1 genes in 12 normal peripheral blood (PB) specimens, seven normal bone marrow (BM) specimens, five lymph node (LN) specimens, and seven leukemic cell lines, and 27 patients with malignant lymphoma (ML), four with acute lymphocytic leukemia (ALL), three with acute myelocytic leukemia (AML), and four with chronic myelocytic leukemia in blastic crisis (CML-BC). Using Northern blot analysis, small amounts of EPR-1 mRNA were detected in normal PB, normal BM and LN specimens, but no Survivin mRNA was detected. However, Survivin mRNA was detected in two of the 12 normal PB, six of the seven normal BM and one of the five LN specimens using reverse transcription and polymerase chain reaction (RT-PCR). Expression of both the Survivin and EPR-1 genes was detected in six of the seven cell line samples by Northern blot, and in all of them by RT-PCR. Mutual expression of the Survivin and EPR-1 genes was detected in three of the four CML-BC samples, 15 of the 27 ML samples, two of the four ALL samples, and all three AML samples using the RT-PCR method. No EPR-1 expression with or without Survivin expression was clearly detected in eight of the nine diffuse large B-cell lymphoma (DLB) specimens, two of the six follicular center lymphoma specimens, one of the four specimens of nodular sclerosis of Hodgkin's lymphoma, two of the four ALL specimens or one of the four CML-BC specimens. The data presented here show that disrupted expression of the Survivin/EPR-1 genes occurred in many kinds of hematologically malignant cells. This may be of biological importance.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Shinozawa
authors.forename: K
authors.initials: K
authors.lastname: Inokuchi
authors.forename: I
authors.initials: I
authors.lastname: Wakabayashi
authors.forename: K
authors.initials: K
authors.lastname: Dan
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002874:Chromosome Mapping; D019337:Hematologic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006689:Hodgkin Disease / Q000097:blood / Q000235:genetics / Q000473:pathology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000235:genetics / Q000473:pathology; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016133:Polymerase Chain Reaction / Q000379:methods; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics / Q000473:pathology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000097:blood / Q000235:genetics*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012697:Serine Endopeptidases / Q000235:genetics; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000077022:Survivin; D012697:Serine Endopeptidases