LEUKEMIC STEM CELLS DEFINED BY DIPEPTIDIL-PEPTIDASE IV (CD26) EXPRESSION IN CD34+CD38- STEM CELLS AND TYROSINE KINASE INHIBITOR THERAPY IN CHRONIC MYELOID LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Rodrigues-Santos P. 06/09/16; 134706; PB1806
Dr. Paulo Rodrigues-Santos
Contributions
Contributions
Abstract
Abstract: PB1806
Type: Publication Only
Background
Recently, dipeptidil-peptidase IV (DPP IV; CD26) has been described as a specific marker of leukemic stem cells (LSC) within the CD34+CD38-Lin- compartment present in chronic myeloid leukemia (CML) patients. These cells seem to be difficult to eradicate by tyrosine kinase inhibitors (TKI), although the efficacy of different generations of TKI remains unknown. In addition, the negative influence of these LSC on optimal therapy responses (time to achieve major molecular response) is under investigation in CML.
Aims
In this study, we aimed at the evaluation of the presence of LSC in chronic phase CML patients to establish the additional parameters to better define the efficacy of different therapeutic strategies.
Methods
Peripheral blood samples from chronic phase CML patients (n=45) under Interferon-alpha 2b (IFN-α 2b), imatinib, dasatinb, nilotinib, bosutinib and ponatinib therapy were analyzed by multi-parametric flow cytometry for the characterization of LSC. Buffy coats (n=3) from healthy blood donors were used as control. Cytokines and chemokines were evaluated in a 34-plex panel by xMAP technology (Luminex®).
Results
Circulating CD34 positive cells were increased in chronic phase CML patients when compared to controls (0.15±0.05% vs 0.06±0.05%). CD26 was found expressed in CML CD34+CD38-Lin- stem cells (12.07±4.14%) and absent in controls. CD26 expression was higher in LSC compared to progenitor cells (MFI 704.6±200.8 vs. 270.4±34.8). We also found SDF-1 significantly overexpressed in CML patients undergoing TKI treatment when compared to IFN-α 2b. An impairment of LSC to respond to SDF-1, associated with less migration to stem cells niche, has been observed, although they express high levels of CXCR4. All of our chronic phase CML patients with detectable LSC in peripheral blood samples needed to change therapy and/or increase TKI dose and the majority of these patients present high or intermediate clinical prognostic risk score (Sokal) on initial evaluation.
Conclusion
Detection of LSC defined by CD26 in CD34+CD38-Lin- stem cells might be an important tool to improve CML treatment strategy in the near future.
Session topic: E-poster
Keyword(s): CD34+ cells, CD38, Chronic myeloid leukemia, Stem cell marker
Type: Publication Only
Background
Recently, dipeptidil-peptidase IV (DPP IV; CD26) has been described as a specific marker of leukemic stem cells (LSC) within the CD34+CD38-Lin- compartment present in chronic myeloid leukemia (CML) patients. These cells seem to be difficult to eradicate by tyrosine kinase inhibitors (TKI), although the efficacy of different generations of TKI remains unknown. In addition, the negative influence of these LSC on optimal therapy responses (time to achieve major molecular response) is under investigation in CML.
Aims
In this study, we aimed at the evaluation of the presence of LSC in chronic phase CML patients to establish the additional parameters to better define the efficacy of different therapeutic strategies.
Methods
Peripheral blood samples from chronic phase CML patients (n=45) under Interferon-alpha 2b (IFN-α 2b), imatinib, dasatinb, nilotinib, bosutinib and ponatinib therapy were analyzed by multi-parametric flow cytometry for the characterization of LSC. Buffy coats (n=3) from healthy blood donors were used as control. Cytokines and chemokines were evaluated in a 34-plex panel by xMAP technology (Luminex®).
Results
Circulating CD34 positive cells were increased in chronic phase CML patients when compared to controls (0.15±0.05% vs 0.06±0.05%). CD26 was found expressed in CML CD34+CD38-Lin- stem cells (12.07±4.14%) and absent in controls. CD26 expression was higher in LSC compared to progenitor cells (MFI 704.6±200.8 vs. 270.4±34.8). We also found SDF-1 significantly overexpressed in CML patients undergoing TKI treatment when compared to IFN-α 2b. An impairment of LSC to respond to SDF-1, associated with less migration to stem cells niche, has been observed, although they express high levels of CXCR4. All of our chronic phase CML patients with detectable LSC in peripheral blood samples needed to change therapy and/or increase TKI dose and the majority of these patients present high or intermediate clinical prognostic risk score (Sokal) on initial evaluation.
Conclusion
Detection of LSC defined by CD26 in CD34+CD38-Lin- stem cells might be an important tool to improve CML treatment strategy in the near future.
Session topic: E-poster
Keyword(s): CD34+ cells, CD38, Chronic myeloid leukemia, Stem cell marker
Abstract: PB1806
Type: Publication Only
Background
Recently, dipeptidil-peptidase IV (DPP IV; CD26) has been described as a specific marker of leukemic stem cells (LSC) within the CD34+CD38-Lin- compartment present in chronic myeloid leukemia (CML) patients. These cells seem to be difficult to eradicate by tyrosine kinase inhibitors (TKI), although the efficacy of different generations of TKI remains unknown. In addition, the negative influence of these LSC on optimal therapy responses (time to achieve major molecular response) is under investigation in CML.
Aims
In this study, we aimed at the evaluation of the presence of LSC in chronic phase CML patients to establish the additional parameters to better define the efficacy of different therapeutic strategies.
Methods
Peripheral blood samples from chronic phase CML patients (n=45) under Interferon-alpha 2b (IFN-α 2b), imatinib, dasatinb, nilotinib, bosutinib and ponatinib therapy were analyzed by multi-parametric flow cytometry for the characterization of LSC. Buffy coats (n=3) from healthy blood donors were used as control. Cytokines and chemokines were evaluated in a 34-plex panel by xMAP technology (Luminex®).
Results
Circulating CD34 positive cells were increased in chronic phase CML patients when compared to controls (0.15±0.05% vs 0.06±0.05%). CD26 was found expressed in CML CD34+CD38-Lin- stem cells (12.07±4.14%) and absent in controls. CD26 expression was higher in LSC compared to progenitor cells (MFI 704.6±200.8 vs. 270.4±34.8). We also found SDF-1 significantly overexpressed in CML patients undergoing TKI treatment when compared to IFN-α 2b. An impairment of LSC to respond to SDF-1, associated with less migration to stem cells niche, has been observed, although they express high levels of CXCR4. All of our chronic phase CML patients with detectable LSC in peripheral blood samples needed to change therapy and/or increase TKI dose and the majority of these patients present high or intermediate clinical prognostic risk score (Sokal) on initial evaluation.
Conclusion
Detection of LSC defined by CD26 in CD34+CD38-Lin- stem cells might be an important tool to improve CML treatment strategy in the near future.
Session topic: E-poster
Keyword(s): CD34+ cells, CD38, Chronic myeloid leukemia, Stem cell marker
Type: Publication Only
Background
Recently, dipeptidil-peptidase IV (DPP IV; CD26) has been described as a specific marker of leukemic stem cells (LSC) within the CD34+CD38-Lin- compartment present in chronic myeloid leukemia (CML) patients. These cells seem to be difficult to eradicate by tyrosine kinase inhibitors (TKI), although the efficacy of different generations of TKI remains unknown. In addition, the negative influence of these LSC on optimal therapy responses (time to achieve major molecular response) is under investigation in CML.
Aims
In this study, we aimed at the evaluation of the presence of LSC in chronic phase CML patients to establish the additional parameters to better define the efficacy of different therapeutic strategies.
Methods
Peripheral blood samples from chronic phase CML patients (n=45) under Interferon-alpha 2b (IFN-α 2b), imatinib, dasatinb, nilotinib, bosutinib and ponatinib therapy were analyzed by multi-parametric flow cytometry for the characterization of LSC. Buffy coats (n=3) from healthy blood donors were used as control. Cytokines and chemokines were evaluated in a 34-plex panel by xMAP technology (Luminex®).
Results
Circulating CD34 positive cells were increased in chronic phase CML patients when compared to controls (0.15±0.05% vs 0.06±0.05%). CD26 was found expressed in CML CD34+CD38-Lin- stem cells (12.07±4.14%) and absent in controls. CD26 expression was higher in LSC compared to progenitor cells (MFI 704.6±200.8 vs. 270.4±34.8). We also found SDF-1 significantly overexpressed in CML patients undergoing TKI treatment when compared to IFN-α 2b. An impairment of LSC to respond to SDF-1, associated with less migration to stem cells niche, has been observed, although they express high levels of CXCR4. All of our chronic phase CML patients with detectable LSC in peripheral blood samples needed to change therapy and/or increase TKI dose and the majority of these patients present high or intermediate clinical prognostic risk score (Sokal) on initial evaluation.
Conclusion
Detection of LSC defined by CD26 in CD34+CD38-Lin- stem cells might be an important tool to improve CML treatment strategy in the near future.
Session topic: E-poster
Keyword(s): CD34+ cells, CD38, Chronic myeloid leukemia, Stem cell marker
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