Lack of the Polycomb-group gene rae28 causes maturation arrest at the early B-cell developmental stage

被引:52
作者
Tokimasa, S
Ohta, H
Sawada, A
Matsuda, Y
Kim, JY
Nishiguchi, S
Hara, J
Takihara, Y
机构
[1] Osaka Univ, Microbial Dis Res Inst, Dept Med Genet & Mol Cell Biol, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Grad Sch Med, Dept Dev Med, Suita, Osaka, Japan
关键词
polycomb-group genes; rae28; B-cell development; 12p acute lymphoblastic leukemia;
D O I
10.1016/S0301-472X(00)00620-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. The rae28 gene (rae28) is a murine homologue of the Drosophila polyhomeotic gene, which is a member of the Polycomb-group genes. In this study, we examined the role of rae28 in lymphocyte development, Materials and Methods. Because homozygous rae28-deficient (rae28(-/-)) mice died in the perinatal period, we examined lymphocyte development by generating chimeric mice reconstituted with green fluorescence protein-labeled mutant fetal liver cells as well as in in vitro culture systems. We further examined RAE28 expression by reverse transcriptase polymerase chain reaction assay in human leukemic cells with B-lineage acute lymphoblastic leukemia (ALL). Results. Severe B-cell maturation arrest was observed in I rae28(-/-) between pro- and pre-B lymphocyte stages. B-cell development was also delayed in heterozygous neonates. Furthermore, interleukin-7-dependent colony-forming ability was impaired not only in homozygous lymphocytes hut also in heterozygotes. Its human homologue, RAE28, is located on chromosome 12p13, which frequently is associated with chromosomal abnormalities and loss of heterozygosity in patients with hematologic malignancies. To determine whether a link exists between RAE28 and leukemia, we examined RAE28 expression in leukemic cells from pediatric patients with B-lineage ALL. RAE28 expression was not detected in four B-cell precursor ALL cases of a total of 43 examined, although RAE28 is normally expressed constitutively during the process of B-cell maturation as assessed in isolated cell populations, Conclusions, rae28 plays an important role in the early B-cell developmental stage in a gene dosage-dependent manner. Furthermore, the human RAE28 locus may provide a candidate gene causing the molecular pathogenesis of childhood B-cell precursor ALL. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.
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页码:93 / 103
页数:11
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