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

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

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.879471

DOI=10.3389/fonc.2022.879471

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>we simultaneously assessed TIM-3 expression levels of leukemic blasts and T lymphocytes in the bone marrow of <italic>de novo</italic> 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.</p></sec><sec><title>Results</title><p>TIM-3 expression of CD34<sup>+</sup> leukemic blasts (R<sup>2 </sup>= 0.95, p&lt;0.0001) and CD34<sup>+</sup>CD38<sup>-</sup> leukemic stem cells (R<sup>2 </sup>= 0.75, p&lt;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<sup>+</sup> (R<sup>2 </sup>= 0.44, <italic>p</italic>&lt;0.0001) and CD4<sup>+</sup> (R<sup>2 </sup>= 0.16, <italic>p</italic>=0.0181) lymphocytes, and higher TIM-3 expression of leukemic blasts was significantly associated with a greater proportion of peripheral CD8<sup>+</sup> T lymphocytes (R<sup>2 </sup>= 0.24, <italic>p</italic>=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%, <italic>p</italic>=0.0012), while TIM-3 expression levels of leukemic blasts were not significantly associated with the remission status after induction chemotherapy (<italic>p</italic>=0.9799), overall survival (<italic>p</italic>=0.4201) or event-free survival (<italic>p</italic>=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, <italic>p</italic>&lt;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%, <italic>p</italic>=0.6660).</p></sec><sec><title>Conclusion</title><p>TIM-3 expression level on AML blasts correlates with presence of CBF translocations rather than clinical outcomes.</p></sec>