AML1-Evi-1 specifically transforms hematopoietic stem cells through fusion of the entire Evi-1 sequence to AML1

被引：13

作者：

Takeshita, M.

Ichikawa, M.

Nitta, E.

Goyama, S.

Asai, T.

Ogawa, S.

Chiba, S. ^{[2
]}

Kurokawa, M. ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Cell Therapy & Transplantat Med, Tokyo 1138655, Japan

来源：

LEUKEMIA | 2008年 / 22卷 / 06期

关键词：

RUNX1; AML1; Evi-1; leukemogenesis;

D O I：

10.1038/leu.2008.53

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The t(3; 21) chromosomal translocation seen in blastic crisis of chronic myeloid leukemia and secondary leukemias results in a formation of a chimeric protein AML1-Evi-1, which suppresses wild-type AML1 function. Loss of AML1 function causes expansion of hematopoietic progenitor cells, whereas it is not sufficient for the development of leukemia. To identify essential mechanisms through which AML1-Evi-1 exerts full leukemogenic potential, we introduced AML1-Evi-1 and its mutants in murine bone marrow cells, and evaluated their transforming activities by colony replating assays. The transforming activity of AML1-Evi-1 was lost when any of the known functional domains of Evi-1 was deleted from the chimeric protein, and forced expression of Evi-1 did not transform the AML1-deleted bone marrow cells. Unlike the MLL-ENL and AML1-ETO leukemia-related chimeric proteins, AML1- Evi-1 could transform only the hematopoietic stem cell fraction. Moreover, AML1-Evi-1-transformed cells show a cell-marker profile distinct from that of the cells transformed by AML1-ETO, which also suppresses AML1 function. Thus, leukemogenic activity of AML1-Evi-1 may be due to activation of molecular mechanisms distinct from those activated by MLL-ENL or AML1-ETO in the hematopoietic stem cell fractions.

引用

页码：1241 / 1249

页数：9

共 32 条

[1] Interaction of EVI1 with cAMP-responsive element-binding protein-binding protein (CBP) and p300/CBP-associated factor (P/CAF) results in reversible acetylation of EVI1 and in co-localization in nuclear speckles [J].