免疫グロブリンH鎖遺伝子の染色体転座と相手遺伝子による多発性骨髄腫の病型分類

2001 Fiscal Year Annual Research Report

• Project/Area Number: 12671001
• Research Institution: KYOTO PREFECTURAL UNIVERSITY OF MEDICINE
• Principal Investigator: 谷脇 雅史 京都府立医科大学, 医学部, 講師 (80163640)
• Co-Investigator(Kenkyū-buntansha): 奥田 司 京都府立医科大学, 医学部, 講師 (30291587)
• Keywords: 蛍光in situ分子雑種法 / 多発性骨髄種 / 免疫グロブリンH鎖遺伝子 / 染色体転座 / 遺伝子診断

Research Abstract

[目的]多発性骨髄腫(MM)におけるIgH遺伝子の転座がBリンパ球のどの分化段階で生じたのかを検討した.[方法]骨髄または末梢血よりFicoll-Paqueで単核細胞を分離し,preB細胞(CD38+,CD19-),幼弱骨髄腫細胞(CD38+,CD19-,MPC-),成熟骨髄腫細胞(CD38+,CD19-,MPC+)をsortingした.分画したこれらの細胞群にDC-FISH法を施行した.[結果]17症例のMMあるいはMGUSを検討し,13例(76.4%)でIgH遺伝子座のSplitを検出した。転座相手は、FGFR3が7例,c-MYCが4例,CCND1が4例であった.また,4例では複数のIgH転座を検出し,FGFR3+CCND1が3例,FGFR3+c-MYCが1例であった.IgH転座の陽性例でも,preB細胞にはIgH遺伝子のsplitは検出されなかった.骨髄腫細胞の成熟度とIgH転座の関連を検討すると,FGFR3を転座相手とした症例では,幼弱骨髄腫細胞にのみ転座が認められた症例と,逆に成熟細胞にのみ転座が認められた症例,幼弱と成熟いずれの細胞群にも転座が認められた症例とが存在した.一方,CCND1を転座相手とする症例では,すべて幼弱と成熟いずれの細胞群にも転座が認められるパターンであった.[結論]FGFR3/IgH転座はBリンパ球の分化成熟段階の早期と後期にも関与するが,CCND1/IgH転座は骨髄腫発生の早期変化と考えられる.Double IgH転座の存在は,がん遺伝子が段階的に転座しMMの発症と進展に関与していることを示唆している.

Research Products

• [Publications] Sakabe H: "A Case of MALT lymphoma at the base of the tongue that developed without any background of immunodeficiency or autoimmune disease"Leuk Lymphoma. (in press).
• [Publications] Okamoto T: "Minimal residual disease in early phase of chemotherapy reflect poor outcome in children with acute lymphoblastic leukemia-A retrospective study by the Children's Cancer and Leukemia Study Group in Japan-"Leuk Lymphoma. (in press).
• [Publications] Ono R: "SEPTIN6, a human homolog to mouse septin6, is fused to MLL in infant acute myeloid leukemia with complx chromosomal abnormalities involving 11q23 and Xq24."Cancer Res. 62(2). 333-337 (2002)
• [Publications] Nomura K: "Differentiation of follicular from mucosa-associated lymphoid tissue lymphoma by detection of t(14;18) on single cell preparations and paraffin-embedded sections"Genes Chromosomes Cancer. 33(2). 213-216 (2002)
• [Publications] Nomura K: "Multiple bone lesions after allogeneic bone marrow transplantation in a patient with relapsed adult acute lymphoblastic leukmia : Minimal residual disease predicts extramedullary relapse"Leuk Lymphoma. 42(6). 1305-1308 (2001)
• [Publications] Yagasaki F: "Fusion of ETV6 to fibroblast growth factor receptor 3 in peripheral T-cell lymphoma with at(4;12)(p16;p13) chromosomal translocation"Cancer Res. 61(23). 8371-8374 (2001)
• [Publications] Kita-Sasai Y: "International prognostic scoring system (IPSS) and TP53 mutations are independent prognostic indicators for patients with myeloysplastic syndrome"Brit J Haematol. 115(2). 309-312 (2001)
• [Publications] Kaneko H: "Clinicopathologic and cytogenetic analyses of three cases of primary uterine non-Hodgkin's lymphoma"Intern Med. 40(10). 1028-1031 (2001)
• [Publications] Otsuki T: "Establishment of CD7+ human myeloma sister cell lines, KMS-21-PE and KMS-21-BM, carrying t(11;14) and t(8;14)"Leuk Lymphoma. 42(4). 761-774 (2001)
• [Publications] Inokuchi K: "Establishment of a cell line with AML1-MTG8, TP53, andTP73 abnormalities from acute myelogenous leukemia"Genes Chromosomes Cancer. 32(2). 182-187 (2001)
• [Publications] Okuda T: "RUNX1/AML1: a central player in hematopoiesis"Int J Hematol. 74(3). 252-257 (2001)
• [Publications] Fujita Y: "Identification of an alternatively spliced form of the mouse AML1/RUNX1 gene transcript AML1c and its expression in early hematopoietic development"Biochem Biophys Res Commun. 281(5). 1248-1255 (2001)
• [Publications] Tamura A: "Interphase detection of immunoglobulin heavy chain translocations with specific oncogene loci in 173 patients with B-cell lymphoma"Cancer Genet Cytogenet. 129(1). 1-9 (2001)
• [Publications] Hanamura I: "Ectopic expression of mafb gene in human myeloma cells carrying (14;20)(q32;q11) chromosomal translocations"Jpn J Cancer Res. 92(6). 638-644 (2001)
• [Publications] Yagita K: "Langerhans cell histiocytosis of an adult with tumors in liver and spleep"Hepatogastroenterology. 48(38). 581-584 (2001)
• [Publications] Hatzivassiliou G: "IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B Cells and involved in chromosome 1 q21 abnormalities in B cell malignancy"Immunity. 14(3). 277-289 (2001)
• [Publications] Jamal R: "Codupulication of the MLL and FLT3 gene in patients with acute myeloid leukemia"Genes Chromosomes Cancer. 31(2). 187-190 (2001)
• [Publications] Tatsumi K: "The CDCREL1 gene fused to MLL in de novo acute myeloed leukemia with t(11;22)(q23; q11.2) and its frequent expression in myeloid leukemia cell lines"Genes Chromosomes Cancer. 30(3). 230-235 (2001)
• [Publications] 谷脇雅史: "血球との対話〜血球を"見る"から"考える"時代へ(吉田弥太郎編)"医薬ジャーナル社. 134 (2001)