title: High MN1 expression increases the in vitro clonogenic activity of primary mouse B-cells.
abstract: The MN1 (Meningioma 1) gene is overexpressed in certain subtypes of acute myeloid leukemia (AML) and high levels of MN1 expression in mouse bone marrow cells results in myeloid leukemia. We showed that compared with control bone marrow (BM) MN1 expression was increased (2-fold or more) in 29 out of 73 (40%) pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient BM. Additional analysis of MN1 expression in sub-groups within our cohort carrying different chromosome translocations showed that carriers of the good prognostic marker t(12;21)(TEL-AML1) (n=27) expressed significantly more MN1 than both healthy controls (n=9) (P=0.02) and the group carrying the t(9;22)(BCR-ABL) (n=9) (P=0.001). In addition, AML1 expression was also upregulated in 31 out of 45 (68%) B-ALL patient BM compared with control and there was a significant correlation between MN1 and AML1 expression (r=0.3552, P=0.0167). Retroviral MN1 overexpression increased the colony forming activity of mouse Pro-B/Pre-B cells in vitro. Our results suggest that deregulated MN1 expression contributes to the pathogenesis of pediatric B-ALL. Further investigation into the clinical and biological significance of elevated MN1 expression in TEL-AML1(positive) leukemia might provide insight into additional molecular mechanisms contributing to B-ALL and may lead to improved treatment options for patients.
authors.affiliation: St Jude Children's Research Hospital, Department of Genetics, Memphis, TN, USA.
authors.forename: Masashi
authors.initials: M
authors.lastname: Numata
authors.affiliation: Gebze Technical University, Department of Molecular Biology and Genetics, Gebze, Kocaeli, Turkey.
authors.forename: Mehmet Deniz
authors.initials: MD
authors.lastname: Yener
authors.affiliation: Institute for Experimental Medicine, Department of Genetics, Istanbul University, Istanbul, Turkey.
authors.forename: Sema Sırma
authors.initials: SS
authors.lastname: Ekmekçi
authors.affiliation: Institute for Experimental Medicine, Department of Genetics, Istanbul University, Istanbul, Turkey.
authors.forename: Müge
authors.initials: M
authors.lastname: Aydın
authors.affiliation: St Jude Children's Research Hospital, Department of Genetics, Memphis, TN, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Grosveld
authors.affiliation: St Jude Children's Research Hospital, Department of Genetics, Memphis, TN, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Cardone
authors.affiliation: St Jude Children's Research Hospital, Department of Genetics, Memphis, TN, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Terranova
authors.affiliation: St Jude Children's Research Hospital, Department of Genetics, Memphis, TN, USA.
authors.forename: Ramon Klein
authors.initials: RK
authors.lastname: Geltink
authors.affiliation: Institute for Experimental Medicine, Department of Genetics, Istanbul University, Istanbul, Turkey.
authors.forename: Uğur
authors.initials: U
authors.lastname: Özbek
authors.affiliation: Gebze Technical University, Department of Molecular Biology and Genetics, Gebze, Kocaeli, Turkey.
authors.forename: Emrah
authors.initials: E
authors.lastname: Özçelik
authors.affiliation: Pediatric Hematology Division of Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Çağrı
authors.initials: Ç
authors.lastname: Güleç
authors.affiliation: Pediatric Hematology Division of Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Sema
authors.initials: S
authors.lastname: Anak
authors.affiliation: Pediatric Hematology Division of Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Serap
authors.initials: S
authors.lastname: Karaman
authors.affiliation: Medical Park Hospitals, Bahçelievler, İstanbul, Turkey.
authors.forename: Gülyüz
authors.initials: G
authors.lastname: Öztürk
authors.affiliation: Medical Park Hospitals, Bahçelievler, İstanbul, Turkey.
authors.forename: Meral
authors.initials: M
authors.lastname: Akbıyık
authors.affiliation: Gebze Technical University, Department of Molecular Biology and Genetics, Gebze, Kocaeli, Turkey. Electronic address: akandilci@hotmail.com.
authors.forename: Ayten
authors.initials: A
authors.lastname: Kandilci
mesh_terms: D000293:Adolescent; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology*; D061251:Primary Cell Culture; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C506524:MN1 protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins
keywords: ALL; AML1; MN1; TEL–AML1