Acute myeloid leukemia (AML) patients with high level of EVI1 are associated with unfavorable overall survival, which was aggravated by simultaneous high expression of ATG7 in these patients.
These revertant Tcmra lymphocytes re-expressed CD45RA+, CCR7+, CD62L + and CD127+, shown improved survivability with longer telomere length, expressed memory properties including higher Eomes to Tbet ratio, and exhibited cytotoxicity against autologous AML blast cells.
We report that Evi1 reduced the maturation of leukemic cells and promoted the abundance, quiescence, and activity of LSCs in an MLL-AF9-driven mouse model of AML. atRA further augmented these effects in an Evi1 dependent manner.
Many studies have reported the potential poor prognostic impact of EVI1 higher expression (EVI1<sup>H</sup>) in the AML patients; however, the conclusions previously reported have not been fully assessed and are still controversial.
Acute Myeloid Leukemia (AML): Upregulation of BAALC/MN1/MLLT11/EVI1 Gene Cluster Relate With Poor Overall Survival and a Possible Linkage With Coexpression of MYC/BCL2 Proteins.
Treatment of EVI1<sup>high</sup> AML cell lines (UCSD/AML1 and Kasumi-3) with PIP/56-1 or PIP/56-2 effectively suppressed GPR56 expression by inhibiting binding of EVI1 to its promoter, leading to suppression of cell growth with increased rates of apoptosis.
RNA remnants underwent gene expression profiling analysis using the AML profiler, which detects chromosomal aberrations: t(8;21), t(15;17), inv(16), mutations (CEBPAdm, ABD-NPM1) and BAALC and EVI1 expression.
Recently, important progress has been made in the delineation of the mechanism by which EVI1 becomes deregulated in inv(3)/t(3;3) as well as the cooperating mutations in this specific subset of AML with dismal prognosis.
Our study demonstrates that the magnitude of reduction in EVI1 expression levels between AML diagnosis and follow-up is not sufficient to allow sensitive detection of minimal residual disease.
Ecotropic virus integration site-1 (EVI-1) gene, locus on chromosome 3 (3q26.2) in the human genome, was first found in the AKXD strain of mice, in a model of retrovirus-induced acute myeloid leukemia (AML) established twenty years ago.
High expression of EVI1 is a negative prognostic indicator of survival in acute myeloid leukemia (AML) irrespective of the presence of 3q26 rearrangements.
As activation of Evi1 has been shown to coincide with NRAS mutations in human acute myeloid leukemia, our murine model recapitulates crucial events in human leukemogenesis.
In this study, the expression of these markers and of EVI1 and CDKN1B was determined using oligonucleotide microarrays in 286 AML comprising all cytogenetic groups.
EVI1 transcriptional activation has been reported in up to 10% of AML patients, even in the absence of 3q26 changes, and is an independent indicator of adverse prognosis.
Particularly, high Evi1 expression defines one of the largest clusters in acute myeloid leukemia and is significantly associated with extremely poor prognosis.