title: Expression and mutation analysis of genes that encode the Myc antagonists Mad1, Mxi1 and Rox in acute leukaemia.
abstract: The Myc antagonists Mad1, Mxi1 and Rox proteins share two highly conserved domains, Sin3-interacting domain (SID) and basic helix-loop-helix leucine zipper domain (bHLHzip), which are essential for these proteins to function during molecular switching from proliferation to differentiation. In an attempt to identify mutations in Mad1, Mxi1 and Rox genes in human haematological malignancies, we screened 10 haematopoietic cell lines, bone marrow mononuclear cells (BMMNC) from 26 patients with haematological malignancies and peripheral blood mononuclear cells (PBMNC) from 30 healthy volunteers, using reverse transcription-polymerase chain reaction, single strand conformation polymorphism analysis and sequencing. Mad1, Mxi1 and Rox genes were expressed in all samples. Four polymorphisms were found in cell lines BMMNC and PBMNC: two in Mad1, one in Mxi1 and one in Rox. Nine missense mutations were detected: two in Mad1 in patients, four in Mxi1 (three in patients and one in KG-1 cell line), and three in Rox in patients. No mutations were detected in PBMNC from healthy volunteers. Among six patients with acute lymphoblastic leukaemia, two had Mxi1 mutations and another two had Rox mutations. These mutations were associated with poorer clinical outcomes. This is the first report to show that Mad1, Mxi1 and Rox genes were expressed and displayed mutations in haematological malignancies.
authors.affiliation: Department of Hematology, Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Guo
authors.forename: Ling
authors.initials: L
authors.lastname: Pan
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Suo
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Niu
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Zhang
authors.forename: Fuxu
authors.initials: F
authors.lastname: Wang
authors.forename: Zuo-Ren
authors.initials: ZR
authors.lastname: Dong
authors.forename: Wanming
authors.initials: W
authors.lastname: Da
authors.forename: Ruzo
authors.initials: R
authors.lastname: Ohno
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D020298:U937 Cells
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C501384:MAD1L1 protein, human; C106465:MNT protein, human; C079440:MXI1 protein, human; C489427:MYC protein, human