Dasatinib Down-regulates the Expression of PD-1 and Enhances Killing pH + Leukemia Stem Cells

• Conditions: Chronic Myeloid Leukemia

• Registration Number: NCT04991532
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief Summary

Research on the mechanism of dasatinib down-regulates the expression of PD-1 in CMV-activated NKG2C+NK cells and enhances killing pH + leukemia stem cells.

Detailed Description

Some patients with CML can withdraw from TKIs after treatment, and the mechanism might be related to the effect of memory NK cells on anti-Ph+ leukemic stem cells (LSCs). Dasatinib affects immune through several pathways including the expression of PD1 in immune cells. Our previous work showed increased NKG2C+ NK cells were found in cases with CMV-DNA+ who suffered Ph+ leukemia and received Dasatinib, and these memory NK cells have anti-LSCs activity. We hypothesize that: CMV infection activates NKG2C+ memory NK cells proliferation; Dasatinib down-regulates the expression of PD1 in PD1+NKG2C+ NK cell subsets and then enhances anti-LSCs activity of these cells. In this study, the effect of Dasatinib on CMV-activated NKG2C+ cell subsets and its mechanism will be studies. Besides, the different NKG2C+ cell subsets on LSCs will be compared. This study might be helpful to clarify the mechanism of TKI withdrawal and to offer foundation for CMV and Ph+ ALL treatment strategies

Study Timeline

• Study Start: 2021-06-20
• Status Verified: 2021-08
• Study First Submitted: 2021-08-03
• Study First Submitted QC: 2021-08-04
• Last Update Submitted: 2021-08-04
• Study First Posted: 2021-08-05
• Last Update Posted: 2021-08-05
• Primary Completion: 2022-10
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 324

Inclusion Criteria

1. Age >18 years old, gender is not limited
2. CML-CP patients treated with TKIs
3. No pregnancy was planned during the treatment

Exclusion Criteria

1.The researcher judged that it was not suitable to participate in this study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
NK cells and T cell activation subsets in CML-CP patients treated with TKI for 2 years	2 years	NK cells and T cell activation subsets in CML-CP patients treated with TKI for 2 years

Trial Locations

Locations (1)

Department of Hematology,Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China