# High IL1R1 expression predicts poor survival and benefit from stem cell transplant in intermediate-risk acute myeloid leukemia from the Leucegene cohort

## TL;DR

High IL1R1 gene expression in some leukemia patients predicts worse survival but better outcomes with stem cell transplants.

## Contribution

IL1R1 expression is shown to predict both poor prognosis and benefit from stem cell transplantation in intermediate-risk AML patients.

## Key findings

- High IL1R1 expression correlates with worse 5-year overall and relapse-free survival in intermediate-risk AML patients.
- Stem cell transplantation significantly improves survival in IL1R1high patients but not in IL1R1low patients.
- IL1R1high patients without FLT3-ITD mutation still benefit from stem cell transplantation.

## Abstract

There is an unmet clinical need to identify patients with acute myeloid leukemia and intermediate-risk cytogenetics who benefit from allogeneic hematopoietic stem cell transplantation in first remission, especially among those without FLT3-ITD mutation.

We analyzed transcriptomic data from the Leucegene cohort composed of 316 patients with acute myeloid leukemia and intermediate-risk cytogenetics who have been treated with intensive chemotherapy. We evaluated associations between gene expression and overall survival or relapse-free survival and we analyzed the interaction between gene expression and allogeneic hematopoietic stem cell transplantation to identify biomarkers that predict the benefit of stem cell transplantation in this subgroup of patients.

We identified high IL1R1 expression (IL1R1high) as a prognostic and predictive marker in the Leucegene cohort. IL1R1high (≥ 2.0 transcripts per million) was associated with older age, monocytic differentiation, higher frequency of FLT3-ITD and RUNX1 mutations and lower frequency of IDH1/2 and bZIP CEBPA mutations. Patients with IL1R1high had lower 5-year overall survival (10% vs 38%, p < 0.01), and higher 5-year cumulative incidence of relapse (76% vs 59%, p < 0.01) than those with low IL1R1 expression. IL1R1high was independently associated with overall survival in multivariable analyses including age, white blood cell count at diagnosis and NPM1, FLT3-ITD, bZIP CEBPA, RUNX1, ASXL1 and DNMT3A mutations (HR 1.78, p < 0.01). Importantly, in landmark analysis, hematopoietic stem cell transplantation in first remission significantly improved 5-year overall survival in patients with IL1R1high (67% vs 27%, HR 0.33, p < 0.01), but not in patients with IL1R1low (62% vs 54%, HR 0.72, p = 0.31), especially among those without FLT3-ITD mutation (48% vs 50%, HR 0.93, p = 0.85). In patients who proceeded to allogeneic hematopoietic stem cell transplantation, the 5-year overall survival was 60% in patients with IL1R1high compared to 56% in patients with IL1R1low confirming that the worse prognosis associated with high expression of IL1R1 was abrogated by stem cell transplantation.

IL1R1 expression is a candidate marker to identify patients with intermediate-risk cytogenetics acute myeloid leukemia at high risk of relapse who benefit from allogeneic hematopoietic stem cell transplantation in first remission.

The online version contains supplementary material available at 10.1186/s40364-025-00827-6.