Gene silencing of the tyrosine phosphatase SHP1 gene by aberrant methylation in leukemias/lymphomas.
High-frequent silencing of hematopoietic cell-specific protein-tyrosine phosphatase SHP1 gene by promoter methylation was detected in various kinds of leukemias and lymphomas, as well as in many hematopoietic cell lines, which is supported by our previous observation of strong decrease of SHP1 mRNA and protein. The promoter methylation of the SHP1 gene was clearly correlated with the clinical stage. Loss of heterozygosity with microsatellite markers near the SHP1 gene was shown in 79% of informative acute lymphoblastic leukemia cases. These results suggest that functional loss of SHP1 is associated with the pathogenesis of leukemias/lymphomas.
Oka
Takashi
T
Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan. oka@md.okayama-u.ac.jp
Ouchida
Mamoru
M
Koyama
Maho
M
Ogama
Yoichiro
Y
Takada
Shinichi
S
Nakatani
Yoko
Y
Tanaka
Takehiro
T
Yoshino
Tadashi
T
Hayashi
Kazuhiko
K
Ohara
Nobuya
N
Kondo
Eisaku
E
Takahashi
Kiyoshi
K
Tsuchiyama
Junjiro
J
Tanimoto
Mitsune
M
Shimizu
Kenji
K
Akagi
Tadaatsu
T
D000208:Acute Disease; D001483:Base Sequence; D019175:DNA Methylation; D015973:Gene Expression Regulation, Leukemic; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007938:Leukemia / Q000201:enzymology / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology / Q000235:genetics; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000235:genetics; D019656:Loss of Heterozygosity; D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases