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HIGH EXPRESSION OF TIM-3 ON BLAST CELLS IS ASSOCIATED WITH GOOD PROGNOSTIC FACTORS IN DE NOVO NON-M3 AML
Author(s): ,
Xiaojin Wu
Affiliations:
The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology,Suzhou,China
,
Liangjing Xu
Affiliations:
The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology,Suzhou,China
,
Jinge Xu
Affiliations:
The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology,Suzhou,China
,
Mingqing Zhu
Affiliations:
The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology,Suzhou,China
,
Chengcheng Fu
Affiliations:
The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology,Suzhou,China
,
Yue Han
Affiliations:
The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology,Suzhou,China
,
Xiaowen Tang
Affiliations:
The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology,Suzhou,China
,
Huiying Qiu
Affiliations:
The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology,Suzhou,China
Depei Wu
Affiliations:
The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology,Suzhou,China
(Abstract release date: 05/19/16) EHA Library. Wu D. 06/09/16; 134544; PB1644
Mr. Depei Wu
Mr. Depei Wu
Contributions
Abstract
Abstract: PB1644

Type: Publication Only

Background
T-cell immunoglobulin and mucin domain-containing molecule3 (Tim-3) represents a novel mechanism of T-cell dysfunction and exhaustion. Tim-3 has also been identified in various solid tumors. However, the role of Tim-3 expression on blast cells in acute leukemia is not well understood.

Aims
In this study, we aimed to explore the role of Tim-3 in patients with de novo acute leukemia and the correlation between Tim-3 and clinicopathological prognosis.

Methods
The study cohort consisted of 121 patients including 76 cases with de novo non-M3 AML  and 45 cases with ALL. These patients’ bone marrow samples were collected and then bone Marrow mononuclear cells (BMCs) were isolated for flow cytometry to detect Tim-3 expression on blast cells. E_LINK3'> clinicopathological prognosis.

Results
According to FAB type, 76 AML patients were diagnosed as M0(n=2), M1(n=16), M2(n=20),M4(n=20),M5(n=16) and M6(n=2), respectively. And ALL group were comprised of 38 cases with B-cell ALL and 7 cases with T-cell ALL. The results came out that Tim-3 expression on blasts in de novo AML patients significantly increased compared with that of ALL patients (P=0.00). Moreover, the frequency of Tim-3 high expression was higher in M4 patient than that in other AML patients according to FAB type (P=0.00). Tim-3 high expression was also closely associated with inv(16) (P=0.01) and C/EBPA mutation (P=0.03). The mutations of the following six genes, i.e., FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, had little to do with the expression of Tim-3. Additionally, it is more likely to find higher level of Tim-3 in low-risk group than in intermediate- and high-risk groups (P=0.04). The expression of Tim-3 was positively correlated with CD13(r=0.33,P=0.02), CD34(r=0.51, P=0.00),CD7(r=0.40, P=0.00) in AML patients. As for the ALL patients, Tim-3 expression significantly increased in the T-ALL group than in the B-ALL group (P=0.00). The expression of Tim-3 in ALL patients was positively correlated with CD34(r=0.32, P=0.00), CD7(r=0.56, P=0.01) and negatively with CD10(r=-0.35,P=0.02), CD19(r=-0.24,P=0.00), CD20(r=-0.31,P=0.01). Tim-3 expression was not significantly associated with potential prognostic factors, including age or cytogenetic risk in ALL patients. AML patients with high Tim-3 expression achieved significantly high CR rate (P=0.01) and then their Tim-3 expression significantly decreased after CR (P=0.00), but such trend did not occur in ALL patients.

Conclusion
These findings suggest that high Tim-3 expression on blast cells is associated with good prognosis and detection of Tim-3 expression may be helpful to predict clinicopathological prognosis in non-M3 AML patients. >

Session topic: E-poster

Keyword(s): Acute myeloid leukemia, Expression, Prognostic factor
Abstract: PB1644

Type: Publication Only

Background
T-cell immunoglobulin and mucin domain-containing molecule3 (Tim-3) represents a novel mechanism of T-cell dysfunction and exhaustion. Tim-3 has also been identified in various solid tumors. However, the role of Tim-3 expression on blast cells in acute leukemia is not well understood.

Aims
In this study, we aimed to explore the role of Tim-3 in patients with de novo acute leukemia and the correlation between Tim-3 and clinicopathological prognosis.

Methods
The study cohort consisted of 121 patients including 76 cases with de novo non-M3 AML  and 45 cases with ALL. These patients’ bone marrow samples were collected and then bone Marrow mononuclear cells (BMCs) were isolated for flow cytometry to detect Tim-3 expression on blast cells. E_LINK3'> clinicopathological prognosis.

Results
According to FAB type, 76 AML patients were diagnosed as M0(n=2), M1(n=16), M2(n=20),M4(n=20),M5(n=16) and M6(n=2), respectively. And ALL group were comprised of 38 cases with B-cell ALL and 7 cases with T-cell ALL. The results came out that Tim-3 expression on blasts in de novo AML patients significantly increased compared with that of ALL patients (P=0.00). Moreover, the frequency of Tim-3 high expression was higher in M4 patient than that in other AML patients according to FAB type (P=0.00). Tim-3 high expression was also closely associated with inv(16) (P=0.01) and C/EBPA mutation (P=0.03). The mutations of the following six genes, i.e., FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, had little to do with the expression of Tim-3. Additionally, it is more likely to find higher level of Tim-3 in low-risk group than in intermediate- and high-risk groups (P=0.04). The expression of Tim-3 was positively correlated with CD13(r=0.33,P=0.02), CD34(r=0.51, P=0.00),CD7(r=0.40, P=0.00) in AML patients. As for the ALL patients, Tim-3 expression significantly increased in the T-ALL group than in the B-ALL group (P=0.00). The expression of Tim-3 in ALL patients was positively correlated with CD34(r=0.32, P=0.00), CD7(r=0.56, P=0.01) and negatively with CD10(r=-0.35,P=0.02), CD19(r=-0.24,P=0.00), CD20(r=-0.31,P=0.01). Tim-3 expression was not significantly associated with potential prognostic factors, including age or cytogenetic risk in ALL patients. AML patients with high Tim-3 expression achieved significantly high CR rate (P=0.01) and then their Tim-3 expression significantly decreased after CR (P=0.00), but such trend did not occur in ALL patients.

Conclusion
These findings suggest that high Tim-3 expression on blast cells is associated with good prognosis and detection of Tim-3 expression may be helpful to predict clinicopathological prognosis in non-M3 AML patients. >

Session topic: E-poster

Keyword(s): Acute myeloid leukemia, Expression, Prognostic factor

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