Proteomic analysis of hematopoietic stem cell-like fractions in leukemic disorders.

作者: Jun Ota , Yoshihiro Yamashita , Katsuya Okawa , Hiroyuki Kisanuki , Shin-ichiro Fujiwara

DOI: 10.1038/SJ.ONC.1206855

关键词: Heat shock proteinMolecular biologyBiologyStem cellProteomicsGeneticsNuclear proteinCarcinogenesisProteomeTranscriptomeHematopoietic stem cell

摘要: DNA microarray analysis has been applied to identify molecular markers of human hematological malignancies. However, the relatively low correlation between abundance a given mRNA and that encoded protein makes it important characterize profile directly, or 'proteome,' malignant cells in addition 'transcriptome.' To proteins specifically expressed leukemias, here we isolated AC133(+) hematopoietic stem cell-like fractions from bone marrow 13 individuals with various leukemic disorders, compared their profiles by two-dimensional electrophoresis. A total 11 differentially spots corresponding 10 independent were detected, peptide fingerprinting combined mass spectrometry these revealed them include NuMA (nuclear associates mitotic apparatus), heat shock proteins, redox regulators. The blasts was significantly related presence complex karyotype anomalies. Conditional expression mouse myeloid cell line resulted induction aneuploidy, cycle arrest G(2)-M phases, apoptosis. These results demonstrate potential proteome background-matched obtained fresh clinical specimens provide insight into mechanism leukemogenesis.

参考文章(26)
Quansheng Du, P. Todd Stukenberg, Ian G. Macara, A mammalian Partner of inscuteable binds NuMA and regulates mitotic spindle organization. Nature Cell Biology. ,vol. 3, pp. 1069- 1075 ,(2001) , 10.1038/NCB1201-1069
J. S. Greenberger, M. A. Sakakeeny, R. K. Humphries, C. J. Eaves, R. J. Eckner, Demonstration of permanent factor-dependent multipotential (erythroid/neutrophil/basophil) hematopoietic progenitor cell lines Proceedings of the National Academy of Sciences of the United States of America. ,vol. 80, pp. 2931- 2935 ,(1983) , 10.1073/PNAS.80.10.2931
Hiroshi Watarai, Yoshimasa Inagaki, Naomi Kubota, Kazumi Fuju, Jun Nagafune, Yasunori Yamaguchi, Toshihiko Kadoya, Proteomic approach to the identification of cell membrane proteins Electrophoresis. ,vol. 21, pp. 460- 464 ,(2000) , 10.1002/(SICI)1522-2683(20000101)21:2<460::AID-ELPS460>3.0.CO;2-P
Hideki Makishima, Fumihiro Ishida, Toshiro Ito, Kiyoshi Kitano, Shuichi Ueno, Ken Ohmine, Yoshihiro Yamashita, Jun Ota, Masao Ota, Kazuyoshi Yamauchi, Hiroyuki Mano, DNA microarray analysis of T cell-type lymphoproliferative disease of granular lymphocytes British Journal of Haematology. ,vol. 118, pp. 462- 469 ,(2002) , 10.1046/J.1365-2141.2002.03646.X
S. Shimoda-Matsubayashi, T. Hattori, H. Matsumine, A. Shinohara, A. Yoritaka, H. Mori, T. Kondo, M. Chiba, Y. Mizuno, Mn SOD activity and protein in a patient with chromosome 6-linked autosomal recessive parkinsonism in comparison with Parkinson's disease and control Neurology. ,vol. 49, pp. 1257- 1262 ,(1997) , 10.1212/WNL.49.5.1257
Toshiro Okuyama, Yoshihiko Maehara, Kazuya Endo, Hideo Baba, Yosuke Adachi, Michihiko Kuwano, Keizo Sugimachi, None, Expression of glutathione s‐transferasepi and sensitivity of human gastric cancer cells to cisplatin Cancer. ,vol. 74, pp. 1230- 1236 ,(1994) , 10.1002/1097-0142(19940815)74:4<1230::AID-CNCR2820740409>3.0.CO;2-0
Yoshihiro Yamashita, Akira Miyazato, Ken-ichi Ohya, Uichi Ikeda, Kazuyuki Shimada, Yasusada Miura, Keiya Ozawa, Hiroyuki Mano, Deletion of Src Homology 3 Domain Results in Constitutive Activation of Tec Protein‐Tyrosine Kinase Japanese Journal of Cancer Research. ,vol. 87, pp. 1106- 1110 ,(1996) , 10.1111/J.1349-7006.1996.TB03118.X
Sunil C. Kaul, Renu Wadhwa, Yoichi Matsuda, Patrick J. Hensler, Olivia M. Pereira-Smith, Yasuhiko Komatsu, Youji Mitsui, Mouse and human chromosomal assignments of mortalin, a novel member of the murine hsp70 family of proteins FEBS Letters. ,vol. 361, pp. 269- 272 ,(1995) , 10.1016/0014-5793(95)00177-B
D A Compton, D W Cleveland, NuMA is required for the proper completion of mitosis. Journal of Cell Biology. ,vol. 120, pp. 947- 957 ,(1993) , 10.1083/JCB.120.4.947