Predictive value of high EVI1 expression in AML patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation in first CR

Abstract

The EVI1 gene is a transcriptional regulator of hematopoietic stem cell self renewal and its overexpression is associated with adverse prognosis in de novo AML. Whether the overexpression of EVI1 also predicts poor outcome of AML patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first CR (CR1) is still unclear. Thirty-two (21.2%) out of 151 patients were categorized as high EVI1 expression (EVI1+), and 119 (78.8%) patients were categorized as low EVI1 expression (EVI1-). The frequency of EVI1+ was much higher in the adverse-risk group than the intermediate-risk group (53% vs 19%, P=0.005). EVI1+ patients were significantly likely to harbor with translocations involving the MLL gene on 11q23 (8/9). Significantly poor results were observed in the EVI1+ cohort in terms of leukemia-free survival (LFS) (in 24 months 52.6 vs 71.0%, P=0.027), overall survival (OS) (in 24 months 52.8 vs 72.4%, P=0.012), and cumulative incidence of relapse (in 24 months 39.5 vs 22.5%, P=0.013). Multivariable analysis revealed that low EVI1 expression as an independent prognostic factor favoring LFS (hazards ratio=0.47, 95% confidence interval 0.26-0.86, P=0.01) but not OS. Our results indicate high EVI1 expression might predict high risk of relapse in AML patients undergoing myeloablative allo-HSCT in CR1.

Efficacy of All-Trans-Retinoic Acid in High-Risk Acute Myeloid Leukemia with Overexpression of EVI1

“…The ecotropic viral integration site 1 ( EVI1 ) gene is a proto-oncogene that encodes a zinc-finger DNA-binding protein previously detected in some AML and myelodysplastic syndromes (MDS) [ 2 , 3 ], but not in normal marrow and cord blood cells. Enhanced expression of EVI1 is associated with a very poor disease outcome [ 4 , 5 ], despite allogeneic hematopoietic stem cell transplantation [ 6 ]. Experimental studies suggest EVI1 blocks cellular differentiation by binding to GATA - 1 or other specific DNA sequences controlling gene expression, and may be involved in the pathogenesis of some AMLs [ 7 ].…”

Chromosome Abnormalities and Hematopoietic Stem Cell Transplantation in Acute Leukemias

“…t(3;3)(q21;q26.2)/inv(3)(q21q26.2) AML with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) is a distinct subtype of AML with recurrent genetic abnormalities. It is commonly refractory to conventional chemotherapy due to EVI1 gene overexpression, thus being associated with poor prognosis [32][33][34][35][36]. Isolated inv(3)/t(3;3) were revealed in 43.7% of such patients [33].…”

“…Of interest is that AML and MDS patients with inv(3)/t(3;3) regardless of blast number have both similar clinical and pathological characteristics and short OS. Complex and monosomal karyotypes were also considered independent negative prognostic factors in AML patients with inv(3)/t(3;3) [36]. Due to low incidence of this poor-risk AML subtype, efficacy of HSCT is still subject to small clinical studies [34][35][36], mainly, with poor results.…”

“…Complex and monosomal karyotypes were also considered independent negative prognostic factors in AML patients with inv(3)/t(3;3) [36]. Due to low incidence of this poor-risk AML subtype, efficacy of HSCT is still subject to small clinical studies [34][35][36], mainly, with poor results. As an example of treatment failure in such cases, we presented a clinical case of a young female with inv(3)(q21q26.2), −7.…”

“…The patient underwent a quantitative monitoring with serial expressions of WT1 and EVI gene levels, as reported earlier [35]. The last large investigation in the field has been published recently [36]. It enrolled 32 transplanted patients in the first remission with overexpression of EVI1 gene, induced by aberrations of 3q26 and 11q23 loci, and 119 control patients with low EVI1 expression.…”