Related Experiment Video
Updated: Nov 29, 2025
Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
Single cell sequencing reveals cell populations that predict primary resistance to imatinib in chronic myeloid
Weilong Zhang1,2, Beibei Yang2, Linqian Weng3
1Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, China.
Abstract:
The treatment of chronic myeloid leukemia (CML), a disease caused by t(9;22)(q34;q11) reciprocal translocation, has advanced largely through the use of targeted tyrosine kinase inhibitors (TKIs). To identify molecular differences that might distinguish TKI responders from non-responders, we performed single cell RNA sequencing on cells (n = 41,723 cells) obtained from the peripheral blood of four CML patients at different stages of treatment to generate single cell expression profiles. Analysis of our single cell expression profiles in conjunction with those previously obtained from the bone marrow of additional CML patients and healthy donors (total = 69,263 cells) demonstrated that imatinib treatment significantly altered leukocyte population compositions in both responders and non-responders, and affected the expression profiles of multiple cell populations, including non-neoplastic cell types. Notably, in imatinib poor-responders, patient-specific pre-treatment unique stem/progenitor cells became enriched in peripheral blood compared to the responders. These results indicate that resistance to TKIs might be intrinsic in some CML patients rather than acquired, and that non-neoplastic immune cell types may also play vital roles in dispersing the responsiveness of patients to TKIs. Furthermore, these results demonstrated the potential utility of peripheral blood as a diagnostic tool in the TKI sensitivity of CML patients.
Insights
Chronic myeloid leukemia (CML) treatment with tyrosine kinase inhibitors (TKIs) reveals intrinsic resistance in some patients. Peripheral blood analysis may predict TKI sensitivity in CML.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Chronic myeloid leukemia (CML) is driven by a specific genetic translocation.
- Tyrosine kinase inhibitors (TKIs) have revolutionized CML treatment.
- Understanding TKI resistance mechanisms is crucial for improving patient outcomes.
Purpose of the Study:
- To identify molecular differences between TKI responders and non-responders in CML.
- To investigate the impact of TKI treatment on cellular composition and gene expression in CML patients.
- To explore the potential of peripheral blood analysis for predicting TKI sensitivity.
Main Methods:
- Single cell RNA sequencing was performed on peripheral blood cells from 4 CML patients.
- Data was integrated with existing bone marrow single cell datasets from CML patients and healthy donors (total 69,263 cells).
- Analysis focused on leukocyte populations, gene expression profiles, and stem/progenitor cell enrichment.
Main Results:
- Imatinib treatment altered leukocyte composition and gene expression in both responders and non-responders.
- Non-neoplastic immune cells were affected by TKI treatment.
- Enrichment of unique pre-treatment stem/progenitor cells in peripheral blood was observed in poor-responders.
Conclusions:
- TKI resistance in CML may be intrinsic, not solely acquired.
- Non-neoplastic immune cells may influence TKI response.
- Peripheral blood analysis shows promise as a diagnostic tool for TKI sensitivity in CML.
