Genome-wide analysis of gene-expression profiles in chronic myeloid leukemia cells using a cDNA microarray

被引:7
作者
Kaneta, Y
Kagami, Y
Tsunoda, T
Ohno, R
Nakamura, Y
Katagiri, T
机构
[1] Univ Tokyo, Mol Med Lab, Ctr Human Genome, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan
[2] Aichi Canc Ctr Hosp, Dept Hematol & Chemotherapy, Chikusa Ku, Nagoya, Aichi 4648681, Japan
[3] RIKEN, Lab Med Informat, SNP Res Ctr, Inst Phys & Chem Res,Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan
关键词
cDNA microarray; chronic myeloid leukemia; molecular target; expression profiles; genome-wide;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
To characterize molecular mechanisms operating in chronic myeloid leukemia (CML) cells with a view toward development of novel therapeutic targets, we analyzed gene-expression profiles of cancer cells from 27 CML patients using a cDNA microarray representing 23,040 human genes. By comparing expression patterns of CML with those of normal cells, we identified 150 genes that were commonly highly up-regulated in CML cells. In addition to 54 genes (34 of them ESTs) whose functions are currently unknown, the upregulated elements included genes encoding cell-cycle regulators, transcriptional activators, transcriptional factors, and protein kinases as well as proteins already known to be induced in CML, such as some hemoglobins, haptoglobin (HP1), and matrix metalloproteinase 9 (MMP-9), a protein involved in tissue remodeling and tumor invasion. On the other hand, our protocol selected 106 genes, including 13 of unknown function, as being commonly significantly downregulated in all phases of CML. The results of semiquantitative RT-PCR experiments with 11 representatives of the up-regulated group supported the reliability of our microarray analysis. These data should provide useful information for finding candidate genes whose products might serve as molecular targets for treatment of CML patients.
引用
收藏
页码:681 / 691
页数:11
相关论文
共 26 条
[1]   MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia [J].
Armstrong, SA ;
Staunton, JE ;
Silverman, LB ;
Pieters, R ;
de Boer, ML ;
Minden, MD ;
Sallan, SE ;
Lander, ES ;
Golub, TR ;
Korsmeyer, SJ .
NATURE GENETICS, 2002, 30 (01) :41-47
[2]   Gastrointestinal stromal tumors. [J].
Blanke C.D. ;
Eisenberg B.L. ;
Heinrich M.C. .
Current Treatment Options in Oncology, 2001, 2 (6) :485-491
[3]   Bcr-Abl inhibition as a modality of CML therapeutics [J].
Buchdunger, E ;
Matter, A ;
Druker, BJ .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2001, 1551 (01) :M11-M18
[4]   Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the philadelphia chromosome. [J].
Druker, BJ ;
Sawyers, CL ;
Kantarjian, H ;
Resta, DJ ;
Reese, SF ;
Ford, JM ;
Capdeville, R ;
Talpaz, M .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (14) :1038-1042
[5]   Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells [J].
Druker, BJ ;
Tamura, S ;
Buchdunger, E ;
Ohno, S ;
Segal, GM ;
Fanning, S ;
Zimmermann, J ;
Lydon, NB .
NATURE MEDICINE, 1996, 2 (05) :561-566
[6]   Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. [J].
Druker, BJ ;
Talpaz, M ;
Resta, DJ ;
Peng, B ;
Buchdunger, E ;
Ford, JM ;
Lydon, NB ;
Kantarjian, H ;
Capdeville, R ;
Ohno-Jones, S ;
Sawyers, CL .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (14) :1031-1037
[7]   Mechanisms of disease - The biology of chronic myeloid leukemia [J].
Faderl, S ;
Talpaz, M ;
Estrov, Z ;
O'Brien, S ;
Kurzrock, R ;
Kantarjian, HM .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 341 (03) :164-172
[8]   CGP57148B (STI-571) induces differentiation and apoptosis and sensitizes Bcr-Abl-positive human leukemia cells to apoptosis due to antileukemic drugs [J].
Fang, GF ;
Kim, CN ;
Perkins, CL ;
Ramadevi, N ;
Winton, E ;
Wittmann, S ;
Bhalla, KN .
BLOOD, 2000, 96 (06) :2246-2253
[9]   Erythropoiesis in the absence of janus-kinase 2:: BCR-ABL induces red cell formation in JAK2-/- hematopoietic progenitors [J].
Ghaffari, S ;
Kitidis, C ;
Fleming, MD ;
Neubauer, H ;
Pfeffer, K ;
Lodish, HF .
BLOOD, 2001, 98 (10) :2948-2957
[10]   Molecular classification of cancer: Class discovery and class prediction by gene expression monitoring [J].
Golub, TR ;
Slonim, DK ;
Tamayo, P ;
Huard, C ;
Gaasenbeek, M ;
Mesirov, JP ;
Coller, H ;
Loh, ML ;
Downing, JR ;
Caligiuri, MA ;
Bloomfield, CD ;
Lander, ES .
SCIENCE, 1999, 286 (5439) :531-537