TIM3 Is Upregulated in Cell Lysates of Patients with Acute Myeloid Leukemia

Background

T-cell immunoglobulin and mucin domain-containing molecule3 (TIM3) is known to be a member of a multiple checkpoint receptors. It is expressed on dysfunctional or 'exhausted' T cells during cancer or chronic viral infection. However, its role in some specific cancers such as acute myeloid leukemia (AML) and its relationship to prognostic factors is still unclear.

Aims

This study aimed to compare the concentrations of TIM3 at the diagnosis and remission stages in acute myeloid leukemia.

Methods

Paired bone marrow and peripheral blood samples of patients with AML were collected at diagnosis and remission after treatment with standard doses of intensive chemotherapy using daunorubicin and cytarabine. Upon collection, cell lysates were obtained from both samples. The concentrations of TIM3 were then estimated using ELISA.

Results

Forty samples for 15 patients with AML and seven healthy controls were included in this study, with 13 men (87%) and two women (13%) with a mean age of 38.2 ± 16.3 years. The healthy controls included four men and three women. For patients, the median hemoglobin and platelet counts at diagnosis were 8.3 g/dL (Range 5 - 14) and 56 *10⁹/L (Range 26 - 198), respectively. The median white blood cells count, peripheral blood blasts percentage, and bone marrow blasts percentage were 26.6 *10⁹/L (Range 1.2 - 213), 49% (Range 3 - 72), and 72% (Range 31 - 91), respectively.

In peripheral blood, TIM3 concentration was significantly higher in patients with AML compared to healthy controls (p = 0.01), with a median concentration of 9.26 pg/ml (Range 0.45- 72.2) in patients and 5.1 pg/ml (Range 4.5-6.6) in healthy controls (Figure 1). In patients, TIM3 concentration of peripheral blood cell lysates was higher at diagnosis compared to remission, with a median concentration of 9.25 pg/ml (Range 0.45 - 72.2) and 5.57 pg/ml (Range 1.86 - 27.2), respectively (p =0.03). In bone marrow cell lysates at diagnosis, TIM3 concentration was higher compared with healthy controls (p = 0.04) with a median concentration of 10.89 pg/ml (Range 8.14 - 39.85) and 5.1 pg/ml (Range 4.5-6.6), respectively. In patients, TIM3 concentration of bone marrow cell lysates was not statistically different at diagnosis than at remission, with a median concentration of 10.8 pg/ml (Range 8.14 - 39.85)and 5.1 pg/ml (Range 4.85 -15.61), respectively (p = 0.1) (Figure 2).

Conclusion

In conclusion, TIM3 is upregulated in cell lysates of patients with AML. Therefore, the reduction of TIM3 in peripheral blood or bone marrow may be used as a minimal residual disease in patients with high TIM3 concentration at diagnosis. These findings should be validated in a larger prospective study.

No relevant conflicts of interest to declare.