Scholarlink

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

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月23日

查看全文
  • Guillaume Richard-Carpentier,
  • François Béliveau,
  • Sandrine Lacoste,
  • Banafsheh Khakipoor,
  • Véronique Lisi,
  • Michael Vladovsky,
  • Miriam Marquis,
  • Jean-François Spinella,
  • Patrick Gendron,
  • Sébastien Lemieux,
  • Vincent-Philippe Lavallée,
  • Guy Sauvageau,
  • Josée Hébert

摘要

Background

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.

Methods

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.

Results

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.

Conclusion

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.