Prognostic significance of TIM-3 expression pattern at diagnosis in patients with t(8;21) acute myeloid leukemia

Abstract

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.

Keywords:

• TIM-3
• t(8;21) acute myeloid leukemia
• T and NK cells
• leukemic stem cells

Author contributions

YZQ designed the study. WMC performed the PCR analysis. JW, LY, FTD, YZW, YC and YRL performed flow cytometry. QJ and HJ collected clinical data. JW, FTD and NX analyzed the data. JW wrote the manuscript. YZQ revised the manuscript. All authors read and approved the final approval.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [82070153].