TIM-3 Expression Level on AML Blasts Correlates With Presence of Core Binding Factor Translocations Rather Than Clinical Outcomes

Jian Hong; Leiming Xia; Zhenqi Huang; Xiaodong Yuan; Xinglin Liang; Jifei Dai; Zhonghui Wu; Li Liang; Min Ruan; Zhangbiao Long; Xin Cheng; Xiaowen Chen; Jing Ni; Jian Ge; Qingsheng Li; Qingshu Zeng; Ruixiang Xia; Yi Wang; Mingzhen Yang

doi:10.3389/fonc.2022.879471

TIM-3 Expression Level on AML Blasts Correlates With Presence of Core Binding Factor Translocations Rather Than Clinical Outcomes

Front Oncol. 2022 Apr 14:12:879471. doi: 10.3389/fonc.2022.879471. eCollection 2022.

Authors

Jian Hong¹, Leiming Xia², Zhenqi Huang¹, Xiaodong Yuan³, Xinglin Liang¹, Jifei Dai¹, Zhonghui Wu¹, Li Liang¹, Min Ruan¹, Zhangbiao Long¹, Xin Cheng¹, Xiaowen Chen¹, Jing Ni¹, Jian Ge¹, Qingsheng Li¹, Qingshu Zeng¹, Ruixiang Xia¹, Yi Wang⁴, Mingzhen Yang^{1

2}

Affiliations

¹ Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
² Department of Hematology, The Forth Affiliated Hospital of Anhui Medical University, Hefei, China.
³ Division of Life Sciences and Medicine, Department of Organ Transplantation Center, Transplant and Immunology Laboratory, The First Affiliated Hospital of University of Science and Technology of China (USTC), University of Science and Technology of China, Hefei, China.
⁴ Department of Oncology, The Third Affiliated Hospital of Anhui Medical University, Hefei, China.

Abstract

Background: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) expresses on leukemic stem and progenitor populations of non-M3 acute myeloid leukemia (AML) as well as T lymphocytes. TIM-3 is thought to be involved in the self-renewal of leukemic stem cells and the immune escape of AML cells, however its correlation with AML prognosis is still controversial and worthy of further investigation.

Methods: we simultaneously assessed TIM-3 expression levels of leukemic blasts and T lymphocytes in the bone marrow of de novo AML patients using flow cytometry. The correlations of TIM-3 expression between leukemic blasts and T lymphocytes and the correlations of TIM-3 expression with various patient parameters were analyzed. In addition, the Cancer Genome Atlas (TCGA) data of AML patients were acquired and analyzed to verify the results.

Results: TIM-3 expression of CD34⁺ leukemic blasts (R² = 0.95, p<0.0001) and CD34⁺CD38^- leukemic stem cells (R² = 0.75, p<0.0001) were significantly and positively correlated with that of the whole population of leukemic blasts. In addition, TIM-3 expression level of leukemic blasts correlated significantly and positively with that of CD8⁺ (R² = 0.44, p<0.0001) and CD4⁺ (R² = 0.16, p=0.0181) lymphocytes, and higher TIM-3 expression of leukemic blasts was significantly associated with a greater proportion of peripheral CD8⁺ T lymphocytes (R² = 0.24, p=0.0092), indicating that TIM-3 on leukemic blasts might alter adaptive immunity of AML patients. Regarding clinical data, the presence of core binding factor (CBF) translocations was significantly correlated with higher TIM-3 expression of leukemic blasts (CBF versus non-CBF, median 22.78% versus 1.28%, p=0.0012), while TIM-3 expression levels of leukemic blasts were not significantly associated with the remission status after induction chemotherapy (p=0.9799), overall survival (p=0.4201) or event-free survival (p=0.9873). Similar to our results, TCGA data showed that patients with CBF translocations had significantly higher mRNA expression level of HAVCR2 (the gene encoding TIM-3) (median, 9.81 versus 8.69, p<0.0001), and as all patients in the cohort were divided into two groups based on the median HAVCR2 expression level, 5-year overall survivals were not significantly different (low versus high, 24.95% versus 24.54%, p=0.6660).

Conclusion: TIM-3 expression level on AML blasts correlates with presence of CBF translocations rather than clinical outcomes.

Keywords: TIM-3; acute myeloid leukemia; core binding factor translocation; flow cytometry; prognosis.