The role of EVI1 gene quantification in AML patients with 11q23/MLL rearrangement after allogeneic hematopoietic stem cell transplantation

Jiang, Shuhui; Fan, Yi; Fang, Yanglan; Chao-zhen, Hou; Chen, Jia; Qiu, Huiying; Chen, Suning; Xu, Yang; Wu, Depei

doi:10.1038/s41409-020-01048-1

Cited by 4 publications

(15 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19,21 In particular, the EVI1-high patients accounted for 96.4% in KMT2A-MLLT4 subgroup patients, which as high as previous data (83.9% and 87.9%, respectively). 19,21 In addition, we found that among 86 AML patients with high KMT2A-PTD expression, only 4 (4.7%) had high EVI1 expression. Our study showed the high-level expression of EVI1 might exclusive with the high-level expression of KMT2A-PTD, at least, to a large extent.…”

Section: Using Evi1 To Predict the Outcomes Of Kmt2a Subtype In Diffe...supporting

confidence: 77%

“…Patients with other KMT2A-r subgroups were classified into the high-risk group. 21 Table 1 lists the comparison of clinical characteristics between the two KMT2A subgroups according to the different risk groups (intermediate vs. high risk). There were more EVI1-high patients in the KMT2A high-risk group than in the intermediate risk group (p < .001).…”

Section: Clinical Characteristics In Different Kmt2a Subtype Groupsmentioning

confidence: 99%

“…Our study include the high-risk Non-KMT2A-MLLT3 group of patients as an independent object of analysis for high EVI1 expression in predicting the prognosis, which was different from previous studies that used the whole KMT2A-r spectrum. 19,21 Currently, although there are diverse options for treatment of AML, including allo-HSCT, chemotherapy, and targeted drugs, allo-HSCT is still the only effective treatment for cure. 33 Our results showed that allo-HSCT was a beneficial prognostic factor for OS and DFS of two KMT2A-r subtypes-intermediate and high risk-in accordance with Jiang et al's conclusion on overall KMT2A-r group (2-year OS and DFS: 63.0% and 57.3%, respectively).…”

Section: Using Evi1 To Predict the Outcomes Of Kmt2a Subtype In Diffe...mentioning

confidence: 99%

“…Our study showed that either for the KMT2A-MLLT3 or Non-KMT2A-MLLT3 group patients, high EVI1 expression had a minor effect on prognosis of patients who underwent chemotherapy as the consolidation regimen, whereas it was a poor prognostic indicator for patients who received allo-HSCT (Figure 2). Jiang et al 21 showed that for the transplanted AML patients with overall KMT2A-r, the EVI1-high group had poorer F I G U R E 2 Using EVI1 to evaluate the prognosis of KMT2A-MLLT3 intermediate risk and non-KMT2A-MLLT3 high-risk group patients who underwent different curative methods (chemotherapy vs. transplant). (A) Overall survival for the KMT2A-MLLT3 and non-KMT2A-MLLT3 group according to EVI1 levels (EVI1-low chemotherapy vs. EVI1-low transplant, p < .001 and p < .001, respectively; EVI1-low chemotherapy vs. EVI1-high chemotherapy, p = .853 and p = .067, respectively; EVI1-low chemotherapy vs. EVI1-high transplant, p < .001 and p < .001, respectively; EVI1-low transplant vs. EVI1-high chemotherapy, p < .001 and p < .001, respectively; EVI1-low transplant vs. EVI1-high transplant, p = .026 and p = .048, respectively; EVI1-high transplant vs. EVI1-high chemotherapy, p < .001 and p < .001, respectively).…”

Section: Using Evi1 To Predict the Outcomes Of Kmt2a Subtype In Diffe...mentioning

confidence: 99%

See 3 more Smart Citations

The adverse impact of ecotropic viral integration site‐1 (EVI1) overexpression on the prognosis of acute myeloid leukemia with KMT2A gene rearrangement in different risk stratification subtypes

Liu

Pan

Gao

et al. 2022

Int J Lab Hematology

View full text Add to dashboard Cite

Introduction: AML patients with KMT2A-MLLT3 and other 11q23 abnormalities belong to the intermediate and high-risk level groups, respectively. Whether the poor prognostic value of Ecotropic Viral Integration site-1 (EVI1) overexpression suits either the subtypes of KMT2A-MLLT3 or Non-KMT2A-MLLT3 AML patients (intermediate and high risk group) needs to be further investigated. Methods:We retrospectively analyzed the clinical characteristics of 166 KMT2A-r and KMT2A-PTD AML patients.Results: For the Non-KMT2A-MLLT3 group, patients in the EVI1-high subgroup had shorter OS and DFS and higher CIR than those in the EVI1-low subgroup (p = .027, p = .018, and p = .020, respectively). Additionally, both KMT2A-MLLT3 and Non-KMT2A-MLLT3 patients who received chemotherapy alone had poorer prognosis than patients who also received allogeneic hematopoietic stem cell transplant (allo-HSCT) regardless of their EVI1 expression level (all p < .001). For transplanted patients with KMT2A-MLLT3 or Non-KMT2A-MLLT3 rearrangement, the EVI1-high subgroup had worse prognosis than the EVI1-low subgroup (all p < .05). The 2-year CIR of the KMT2A-MLLT3 and Non-KMT2A-MLLT3 groups with high EVI1 expression was high (52% and 49.6%, respectively). However, for patients with low EVI1 expression, the 2-year CIR of transplanted patients with KMT2A-MLLT3 and Non-KMT2A-MLLT3 was relatively low.Conclusions: Our study showed that for the Non-KMT2A-MLLT3 group, the EVI1-high group had shorter OS and DFS than the EVI1-low group. High EVI1 expression showed an adverse effect in AML with KMT2A rearrangement in different risk stratification subtypes. For the EVI1-high patients with non-KMT2A-MLLT3 rearrangement, other novel regimens towards relapse should be taken into consideration.

show abstract

Section: Using Evi1 To Predict the Outcomes Of Kmt2a Subtype In Diffe...supporting

confidence: 77%

Section: Clinical Characteristics In Different Kmt2a Subtype Groupsmentioning

confidence: 99%

Section: Using Evi1 To Predict the Outcomes Of Kmt2a Subtype In Diffe...mentioning

confidence: 99%

Section: Using Evi1 To Predict the Outcomes Of Kmt2a Subtype In Diffe...mentioning

confidence: 99%

See 2 more Smart Citations

The adverse impact of ecotropic viral integration site‐1 (EVI1) overexpression on the prognosis of acute myeloid leukemia with KMT2A gene rearrangement in different risk stratification subtypes

Liu

Pan

Gao

et al. 2022

Int J Lab Hematology

View full text Add to dashboard Cite

show abstract

“…The major limitations of this study were its retrospective design, single-centre design, and limited sample size. Previous reports have indicated that AML with t(9,11) is associated with a better prognosis than other 11q23 abnormalities [6], and the expression of ecotropic viral integration site 1(EVI1) or fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation was a poor prognostic factor [23,43]. The factors in this study were not significant.…”

Section: Discussioncontrasting

confidence: 63%

Outcomes of allogeneic haematopoietic stem cell transplantation for paediatric patients with MLL-rearranged acute myeloid leukaemia

et al. 2022

View full text Add to dashboard Cite

Background The presence of mixed-lineage leukaemia rearrangement (MLL-r) in paediatric patients with acute myeloid leukaemia (AML) is a poor prognostic predictor. Whether allogeneic haematopoietic stem cell transplantation (allo-HSCT) is beneficial in such cases remains unclear. Methods We evaluated the outcomes and prognostic factors of allo-HSCT in 44 paediatric patients with MLL-r AML in the first complete remission (CR1) between 2014 and 2019 at our institution. Results For all the 44 patients, the 3-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 74.5%, 64.1%, and 29.1%, respectively. Among them, 37 (84.1%) patients received haploidentical (haplo)-HSCT, and the 3-year OS, EFS, and CIR were 73.0%, 65.6%, and 26.4%, respectively. The 100-day cumulative incidence of grade II–IV acute graft-versus-host disease (aGVHD) post-transplantation was 27.3%, and that of grade III–IV aGVHD was 15.9%. The overall 3-year cumulative incidence of chronic graft-versus-host disease (cGVHD) post-transplantation was 40.8%, and that of extensive cGVHD was 16.7%. Minimal residual disease (MRD)-positive (MRD +) status pre-HSCT was significantly associated with lower survival and higher risk of relapse. The 3-year OS, EFS, and CIR differed significantly between patients with MRD + pre-HSCT (n = 15; 48.5%, 34.3% and 59%) and those with MRD-pre-HSCT (n = 29; 89.7%, 81.4% and 11.7%). Pre-HSCT MRD + status was an independent risk factor in multivariate analysis. Conclusions Allo-HSCT (especially haplo-HSCT) can be a viable strategy in these patients, and pre-HSCT MRD status significantly affected the outcomes.

show abstract

Integration of Transcriptomic Features to Improve Prognosis Prediction of Pediatric Acute Myeloid Leukemia With KMT2A Rearrangement

Li,

Zong,

Wan

et al. 2023

HemaSphere

View full text Add to dashboard Cite

Lysine methyltransferase 2A-rearranged acute myeloid leukemia (KMT2A-r AML) is a special entity in the 2022 World Health Organization classification of myeloid neoplasms, characterized by high relapse rate and adverse outcomes. Current risk stratification was established on the treatment response and translocation partner of KMT2A. To study the transcriptomic feature and refine the current stratification of pediatric KMT2A-r AML, we analyzed clinical and RNA sequencing data of 351 patients. By implementing least absolute shrinkage and selection operator algorithm, we identified 7 genes (KIAA1522, SKAP2, EGFL7, GAB2, HEBP1, FAM174B, and STARD8) of which the expression levels were strongly associated with outcomes. We then developed a transcriptome-based score, dividing patients into 2 groups with distinct gene expression patterns and prognosis, which was further validated in an independent cohort and outperformed the LSC17 score. We also found cell cycle, oxidative phosphorylation, and metabolism pathways were upregulated in patients with inferior outcomes. By integrating clinical characteristics, we proposed a simple-to-use prognostic scoring system with excellent discriminability, which allowed us to distinguish allogeneic hematopoietic stem cell transplantation candidates more precisely. In conclusion, pediatric KMT2A-r AML is heterogenous on transcriptomic level and the newly proposed scoring system combining clinical characteristics and transcriptomic features can be instructive in clinical routines.

show abstract

The role of EVI1 gene quantification in AML patients with 11q23/MLL rearrangement after allogeneic hematopoietic stem cell transplantation

Cited by 4 publications

References 31 publications

The adverse impact of ecotropic viral integration site‐1 (EVI1) overexpression on the prognosis of acute myeloid leukemia with KMT2A gene rearrangement in different risk stratification subtypes

The adverse impact of ecotropic viral integration site‐1 (EVI1) overexpression on the prognosis of acute myeloid leukemia with KMT2A gene rearrangement in different risk stratification subtypes

Outcomes of allogeneic haematopoietic stem cell transplantation for paediatric patients with MLL-rearranged acute myeloid leukaemia

Integration of Transcriptomic Features to Improve Prognosis Prediction of Pediatric Acute Myeloid Leukemia With KMT2A Rearrangement

Contact Info

Product

Resources

About