Unknown

Dataset Information

0

EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs.


ABSTRACT: The proto-oncogene EVI1 (ecotropic viral integration site-1), located on chromosome band 3q26, is aberrantly expressed in human acute myeloid leukemia (AML) with 3q26 rearrangements. In the current study, we showed, in a large AML cohort carrying 11q23 translocations, that ? 43% of all mixed lineage leukemia (MLL)-rearranged leukemias are EVI1(pos). High EVI1 expression occurs in AMLs expressing the MLL-AF6, -AF9, -AF10, -ENL, or -ELL fusion genes. In addition, we present evidence that EVI1(pos) MLL-rearranged AMLs differ molecularly, morphologically, and immunophenotypically from EVI1(neg) MLL-rearranged leukemias. In mouse bone marrow cells transduced with MLL-AF9, we show that MLL-AF9 fusion protein maintains Evi1 expression on transformation of Evi1(pos) HSCs. MLL-AF9 does not activate Evi1 expression in MLL-AF9-transformed granulocyte macrophage progenitors (GMPs) that were initially Evi1(neg). Moreover, shRNA-mediated knockdown of Evi1 in an Evi1(pos) MLL-AF9 mouse model inhibits leukemia growth both in vitro and in vivo, suggesting that Evi1 provides a growth-promoting signal. Using the Evi1(pos) MLL-AF9 mouse leukemia model, we demonstrate increased sensitivity to chemotherapeutic agents on reduction of Evi1 expression. We conclude that EVI1 is a critical player in tumor growth in a subset of MLL-rearranged AMLs.

SUBMITTER: Bindels EM 

PROVIDER: S-EPMC3382941 | BioStudies | 2012-01-01

REPOSITORIES: biostudies

Similar Datasets

2013-01-01 | S-EPMC4693300 | BioStudies
2009-01-01 | S-EPMC2656267 | BioStudies
2011-01-01 | S-EPMC3329803 | BioStudies
1000-01-01 | S-EPMC2647665 | BioStudies
2016-01-01 | S-EPMC4911927 | BioStudies
2018-01-01 | S-EPMC5916000 | BioStudies
2017-01-01 | S-EPMC5501293 | BioStudies
2013-01-09 | E-GEOD-43333 | ArrayExpress
2013-01-01 | S-EPMC3754879 | BioStudies
2019-01-01 | S-EPMC6784514 | BioStudies