2000 Fiscal Year Annual Research Report
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
Project/Area Number |
12671001
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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)
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Co-Investigator(Kenkyū-buntansha) |
奥田 司 京都府立医科大学, 医学部, 講師 (30291587)
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Keywords | 蛍光in situ分子雑種法 / 多発性骨髄腫 / 免疫グロブリンH鎖遺伝子 / 染色体転座 / 遺伝子診断 |
Research Abstract |
多発性骨髄腫(MM)107例,形質細胞性白血病4例,形質細胞腫2例の計113例を対象に,IGH遺伝子の染色体転座を解析した.(対象と方法)男性58/女性55例.M蛋白は,IgGκ52例,IgGλ26例,BJκ12例,BJλ10例,IgAκ8例,IgAλ5例.腫瘍細胞の比率は12〜100%.骨髄液,末梢血,胸水を型のごとく固定し,double-color FISH(DC-FISH)を施行した.IgH.転座の陽性例では,PRAD1,c-MYC,FGFR3,MUM1(IRF4),BCL2遺伝子との融合を検討した.(結果)評価が可能であった105例中69例(66%)にIgH遺伝子のスプリットを認めた.t(11;14)をPRAD1/IgHの融合として検出し,評価が可能であった38例のうち27例(71%)で陽性であった.t(8;14)はc-MYC/IgHの融合として検出し35例中11例(31%)が,t(4;14)はFGFR3/IgH融合として検出し48例中8例(17%)が,t(6;14)はMUM1/IgH融合として検出し38例中8例(21%)が陽性であった.PRAD1,c-MYC,FGFR3の全てについて転座相手を検討できた43症例のうち9例(21%)で,2種類のIGH転座を認めた.FGFR3/IgH陽性例8例中7例では,RT-PCRでFGFR3の過剰発現を認めた.FGFR3転座例では骨病変を示す症例が有意に多かった.(考察)MMの66%にIgH転座を認め,t(11;14)とt(8;14)の頻度が高頻度であった.同一症例で2種類の転座相手の見出される場合があり,IgH遺伝子座の不安定性がMMの病因に密接に関与していると考えられる.
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Research Products
(24 results)
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[Publications] Tamura A: "Interphase Detection of IGH Translocations with Specific Oncogene Loci in 173 Patientwith B-cell lymphoma"Cancer Genet Cytogenet. (in press).
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[Publications] Jamal R: "Codupulication of the MLL and FLT3 gene in patients with acute myeloid leukemia"Genes Chromosomes Cancer. (in press).
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[Publications] Tatsumi K: "The CDCREL1 gene fused to MLL in de novo acute myeloid 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)
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[Publications] Kuroda J: "Myelodysplastic Syndrome with Clonal Eosinophilia Accompanied by Eosinophilic Pulmonary Interstitial Infiltration"Acta Haematol. 104・2-3. 119-123 (2000)
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[Publications] Kuroda J: "c-myc overexpression is not mandatory in aggressive-phase multiple myeloma with Burkitt's type translocation"Ann Hematol. 79・9. 514-518 (2000)
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[Publications] Miura I: "Detection of t(14;18) in hyperdipoid cells by fluorescence in situ hybridization in a patient with Hodgkin's disease"Cancer Genet Cytogenet. 123・2. 97-101 (2000)
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[Publications] Mochizuki N: "A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells"Blood. 96・9. 3209-3214 (2000)
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[Publications] Iida S: "A novel human multiple myeloma-derived cell line, NCU-MM-1, carrying t(2;11)(p11;q23) and t(8;22)(q24;q11) chromosomal translocations with overexpression of c-MYC protein.1-128,2000"Int J Hematol. 72・1. 85-91 (2000)
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[Publications] Itoh K: "Randomized comparison of mobilization kinetics of circulating CD34+ cells between biweekly CHOP and dose-escalated CHOP with the prophylactic use of lenograstim (glycosylated rHuG-CSF) in aggressive non-Hodgkin's lymphoma"The Lenograstim/Lymphoma Study Group.Leuk Lymphoma. 38・5-6. 521-532 (2000)
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[Publications] Muto T: "Isolation, tissue distribution, and chromosomal localization of the human activation-induced cytidine deaminase (AID) gene"Genomics. 68・1. 85-88 (2000)
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[Publications] Yamamoto K: "Interstitial Deletion of the Short Arm of Chromosome 12 during Clonal Evolution in myelodysplastic Syndrome with t(5;12)(q13;p13) Involving the ETV6 Gene"Cancer Genet Cytogenet. 119・2. 113-117 (2000)
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[Publications] Yang HW: "The p73 gene is less involved in the development but involved in the progression of neuroblastoma"Int J Mol Med. 5・4. 379-384 (2000)
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[Publications] Miwa H: "Induction of chromosomal aberrations and growth-transformation of lymphoblastoid cell lines by inhibition of reactive oxygen species-induced apoptosis with interleukin-6"Lab Invest. 80・5. 725-734 (2000)
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[Publications] Otsuki T: "Genetic and biological characterization of human myeloma cell lines : A review of the lines established at Kawasaki Medical School"Gene Function and Disease. 1・1. 148-156 (2000)
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[Publications] Hosokawa Y: "The Ikaros gene, a central regulator of lymphoid differentiation, fuses to the BCL6 gene as a result of t (3;7)(q27;p12) translocation in a patient with diffuse large B-cell lymophoma"Blood. 95・8. 2719-2721 (2000)
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[Publications] Nakazawa N: "Interphase detection of t (4;14)(p16.3;q32.3) by in situ hybridization and FGFR3 overexpression in plasma cell malignancies"Cancer Genet Cytogenet. 117・2. 89-96 (2000)
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[Publications] Sugita K: "MLL-CBP fusion transcript in a therapy-related acute myeloid leukemia withe th t (11;16) (q23;p13) which developed in an acule lymphoblastic leukemia patient with fanconi anemia"Genes Chromosomes Cancer. 27・3. 264-269 (2000)
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[Publications] Shimizu S: "Identification of breakpoint cluster regions at 3q21 and 1p36.3 in hematological malignancies with t (1;3)(p36;q21)"Genes Chromosomes Cancer. 27・3. 229-238 (2000)
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[Publications] 西田一弘: "遺伝子解析-FISH法"血液・腫瘍科. 40・suppl3. 431-439 (2000)
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[Publications] 谷脇雅史: "臨床家のための悪性リンパ腫の病態-新しい検査法による病態の解明(特集 白血病とリンパ腫-最新の臨床知見と最新の治療)"Medical Practice. 10・8. 1323-1327 (2000)
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[Publications] 植田豊: "正しい診断をえるために-遺伝子検査(特集 悪性リンパ腫-正しい診断と最高の治療を目指して)"内科. 86・3. 481-484 (2000)
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[Publications] 西田一弘: "SKY法(連載 新しい分子生物学の手法)"分子細胞治療. 1・5. 54(490)-59(495) (2000)
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[Publications] 谷脇雅史: "血球におけるin situ分子雑種法の応用-間期核と細胞レベルの染色体遺伝子解析特集「血球を見る」時代から「血球で考える」時代へ"血液フロンテイア. 10・5. 75-81 (2000)
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[Publications] 谷脇雅史: "染色体分析(生涯教育シリーズ54 血液疾患診療マニュアル)"日本医師会雑誌特別号. 124・8. S114-S116 (2000)