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Summary Wilms' tumour 1 (WT1) can function as an oncogene or a tumour suppressor. Our previous clinical cohort studies showed that low WT1 expression at diagnosis independently predicted poor outcomes in acute myeloid leukaemia (AML) with RUNX1::RUNX1T1, whereas it had an opposite role in AML with non‐favourable cytogenetic risk (RUNX1::RUNX1T1‐deficient). The molecular mechanism by which RUNX1::RUNX1T1 affects the prognostic significance of WT1 in AML remains unknown. In the present study, first we validated the prognostic significance of WT1 expression in AML. Then by using the established transfected cell lines and xenograft tumour model, we found that WT1 suppresses proliferation and enhances effect of cytarabine in RUNX1::RUNX1T1(+) AML but has opposite functions in AML cells without RUNX1::RUNX1T1. Furthermore, as a transcription factor, WT1 physically interacts with RUNX1::RUNX1T1 and acts as a co‐factor together with RUNX1::RUNX1T1 to activate the expression of its target gene DUSP6 to dampen extracellular signal‐regulated kinase (ERK) activity. When RUNX1::RUNX1T1‐deficient, WT1 can activate the mitogen‐activated extracellular signal‐regulated kinase/ERK axis but not through targeting DUSP6. These results provide a mechanism by which WT1 together with RUNX1::RUNX1T1 suppresses cell proliferation through WT1/DUSP6/ERK axis in AML. The current study provides an explanation for the controversial prognostic significance of WT1 expression in AML patients. [ABSTRACT FROM AUTHOR]

Abnormally high ecotropic viral integration site 1 (EVI1) expression has been recognized as a poor prognostic factor in acute myeloid leukemia patients. However, its prognostic impact in B cell precursor acute lymphoblastic leukemia (BCP-ALL) remains unknown. A total of 176 pediatric Ph-negative BCP-ALL patients who received at least 1 course of chemotherapy and received chemotherapy only during follow-up were retrospectively tested for EVI1 transcript levels by real-time quantitative PCR at diagnosis, and survival analysis was performed. Clinical and EVI1 expression data of 129 pediatric BCP-ALL patients were downloaded from therapeutically applicable research to generate effective treatments (TARGET) database for validation. In our cohort, the median EVI1 transcript level was 0.33% (range, 0.0068–136.2%), and 0.10% was determined to be the optimal cutoff value for patient grouping by receiver operating characteristic curve analysis. Low EVI1 expression (<0.10%) was significantly related to lower 5-year relapse-free survival (RFS) and overall survival (OS) rates (P = 0.017 and 0.018, respectively). Multivariate analysis showed that EVI1 expression <0.10% was an independent adverse prognostic factor for RFS and OS. TARGET data showed that low EVI1 expression tended to be related to a lower 5-year OS rate (P = 0.066). In conclusion, low EVI1 expression at diagnosis could predict poor outcomes in pediatric Ph-negative BCP-ALL patients receiving chemotherapy. Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1939818. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease and needs to be stratified. Both, cancer cells and immune cells participate in tumor initiation, growth and progression and might affect clinical outcomes. TIM-3 (T cell immunoglobulin and mucin domain-containing protein 3), an immune checkpoint molecule, is expressed not only on immune cells but also on leukemic stem cells (LSCs) in AML. This prompted us to investigate the prognostic significance of TIM-3 in t(8;21) AML. A total of 47 t(8;21) AML patients were tested for TIM-3 expression by multi-parameter flow cytometry at diagnosis. 35 of these, who received chemotherapy alone or along with allogeneic hematopoietic stem cell transplantation were followed up. The expression pattern of TIM-3 on T-cells and NK (natural killer) cells as a whole (T + NK) and LSCs were evaluated independently. High percentage of T + NK − TIM-3+ and CD34+CD38−TIM-3+ cells were significantly associated with a high 2-year cumulative incidence of relapse (CIR) (p = 0.028, 0.016). Further, concurrent high frequencies of T + NK-TIM-3+ and CD34+CD38-TIM-3+ cells at diagnosis were significantly associated with a high 2-year CIR (p < 0.0001) and this together with c-KIT D816 mutation were the independent adverse prognostic factors for relapse (hazard ratio (HR)=2.5, [95% confidence interval (CI), 1.1–6.0], p = 0.04; HR = 46.5, [95% CI, 2.7–811.5], p = 0.009). In conclusion, the expression pattern of TIM-3 on both T and NK cells and LSCs at diagnosis had prognostic significance in t (8;21) AML. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia with intermediate cytogenetic risk (ICR-AML) needs to be stratified and abnormal gene expression might be prognostic. PR/SET domain 16 (PRDM16) transcript levels were assessed in 267 consecutive adult ICR-AML patients at diagnosis by real-time quantitative PCR. 38.2% patients had PRDM16 transcript levels higher than the upper limit of normal bone marrow samples. Through ROC curve analysis and comparison of relapse-free survival (RFS), the optimal cutoff value of PRDM16 transcript levels was identified to group patients into high expression (PRDM16-H, 21.3%) and low expression (PRDM16-L). PRDM16-H was significantly associated with lower 4-year RFS and overall survival (OS) rates in the entire cohort, patients with normal karyotypes, FLT3-ITD (-) and NPM1 mutation (+)/FLT3-ITD (–) patients (all p <.05). Multivariate analysis showed that PRDM16-H was an independent adverse prognostic factor for RFS and OS in the entire cohort. Therefore, high PRDM16 expression at diagnosis predicts poor outcomes in adult ICR-AML patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the predict significance of the high aldehyde dehydrogenase activity (ALDH + ) propitiation to the relapse of t(8;21) acute myeloid leukemia(AML) patients before and after treatment., Methods: Bone marrow samples of 23 t(8;21) AML patients diagnosis and achieved complete remission in our hospital from April 2015 to June 2016 were collected, then flow cytometry method was used to detect the activity of ALDH, relationship between it and relapse was analyzed., Results: All the patients were followed up for a median of 32 (2-52) months. The median percentage of CD34 + CD38 - and CD34 + CD38 - ALDH + cells among nucleated cells were 2.7 (0.36-35.7)% and 0.017 (0.0013-0.62)% at diagnosis, respectively. Among the bone marrow samples in patients achieved CR, the median percentage of CD34 + CD38 - cells was 0.035 (0.0064-0.66)%, and it was significantly decreased as compared with the percentage at diagnosis (P<0.001); The median percentage of CD34 + CD38 - ALDH + cells was 0.014 (0.0019-0.24)%, and it showed no different as compared with the percentage at diagnosis (P=0.45). Survival analysis showed that patients with higher percentage of CD34 + CD38 - and CD34 + CD38 - ALDH + cells at diagnosis tended to the lower 3-year relapse-free survival (RFS) (P=0.27 and 0.21). Furthermore, patients with higher percentage of CD34 + CD38 - and CD34 + CD38 - ALDH + cells when achieved CR had a significant lower 3-year RFS rates (P=0.010 and 0.0044) as compared with those with lower percentage of CD34 + CD38 - and CD34 + CD38 - ALDH + cells. Multivariate analysis showed that higher percentage of CD34 + CD38 - ALDH + cells when achieved CR was an independent factor affecting RFS of the patients., Conclusion: The percentage of CD34 + CD38 - ALDH + cells at CR in t(8;21) AML patients could predicts relapse, and had more profound predictive significance for relapse than the percentage of CD34 + CD38 - cells.