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Yuan Kong - One of the best experts on this subject based on the ideXlab platform.

  • cd38 cd58 is an independent adverse prognostic factor in paediatric philadelphia chromosome negative b cell acute lymphoblastic leukaemia patients
    Leukemia Research, 2016
    Co-Authors: Leping Zhang, Yazhe Wang, Yazhen Qin, Honghu Zhu, Yueyun Lai, Yuan Kong, Xiaojun Huang, Yan Chang, Yanrong Liu
    Abstract:

    To explore new risk predictors for a high risk of relapse in Philadelphia chromosome negative (Ph-) B cell acute lymphoblastic leukaemia (B-ALL) patients, 196 paediatric Ph- B-ALL patients (≤ 18 years) were retrospectively analysed. We mainly focus on investigating the prognostic value of CD38 and CD58 expression in leukemic blasts in these patients by four colour flow cytometry. The CD38+ CD58- group (n=16) had a higher relapse rate, a shorter 3-year event-free survival (EFS) and overall survival (OS) than the CD38+ CD58+ group (n=157; 31.3% vs 10.2%, P=0.04; 52.4% vs 92.3%, P<0.01; 32.5% vs 91.0%, P=0.01); CD38+ CD58- was an independent adverse prognostic predictor for relapse (hazard ratio [HR], 0.203; 95%CI, 0.063-0.656; P=0.01), 3-year EFS (HR, 0.091; 95%CI, 0.023-0.355; P<0.01) and OS (HR, 0.102; 95%CI, 0.026-0.3971; P<0.01) in this cohort, as determined by Cox multivariate analysis. We identified, for the first time, a higher risk population of paediatric Ph- B-ALL patients with CD38+ CD58- who had a higher relapse risk and a shorter survival. Our results may allow better risk stratification and individualized treatment.

  • presence of cd34 cd38 cd58 leukemia propagating cells at diagnosis identifies patients at high risk of relapse with ph chromosome positive all after allo hematopoietic sct
    Bone Marrow Transplantation, 2015
    Co-Authors: Yuan Kong, Yingjun Chang, Qian Jiang, Hao Jiang, Yazhen Qin, Yong Liu, Yuanwei Sun, Yangyuan Wang, Huan Chen, Xiaojun Huang
    Abstract:

    Relapse of Ph chromosome-positive ALL (Ph+ALL) results from the persistence of leukemia-propagating cells (LPCs). In Ph+ALL, a xenograft assay recently determined that LPCs are enriched in the CD34+CD38−CD58− fraction. Therefore, the prognostic significance of LPCs in Ph+ALL subjects after allogeneic hematopoietic SCT (allo-HSCT) was investigated. A total of 80 consecutive adults with Ph+ALL who underwent allo-HSCT were eligible. A multi-parameter flow cytometry analysis examining CD58–FITC/CD10–PE/ CD19–APC–Cy7/CD34–PerCP/CD45–Vioblue/ CD38–APC on gated leukemia BM blasts was performed at diagnosis. Based on the original blast phenotypes, subjects were stratified into the CD34+CD38−CD58−group (N=15) and other phenotype group (N=65). During minimal residual disease monitoring, significantly higher levels of BCR/ABL transcripts were detected in subjects in the CD34+CD38−CD58− group than in other phenotype group, especially at 3 months post HSCT. In addition, CD34+CD38−CD58−LPCs are directly correlated with a higher 3-year cumulative incidence of relapse (CIR) and worse leukemia-free survival (LFS) and OS. Multivariate analyses indicated that presence of CD34+CD38−CD58− LPCs at diagnosis, and BCR–ABL reduction at 3 months post HSCT were independent risk factors for relapse, LFS and OS. Our data suggest that presence of CD34+CD38−CD58− LPCs at diagnosis allows rapid identification of high-risk patients for relapse after allo-HSCT.

  • cd34 cd38 cd58 leukemia propagating cells at diagnosis could identify patients at high risk for relapse in philadelphia chromosome positive acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation
    Blood, 2014
    Co-Authors: Yuan Kong, Yingjun Chang, Yanrong Liu, Qian Jiang, Hao Jiang, Yazhen Qin, Huan Chen, Yuqian Sun, Yu Wang, Xiaojun Huang
    Abstract:

    Background: Relapse of Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph + ALL) may result from the persistence of leukemia stem cells sometimes termed leukemia-propagating cells (LPCs). We recently found that Ph + ALL LPCs are enriched in the CD34 + CD38 - CD58 - fraction using anti-CD122-conditioned NOD/SCID xenograft assay by intra-bone marrow injection, which translating to adverse clinical outcomes (Kong Y, et al. Leukemia 2014. accepted). Despite the widespread use of abelson tyrosine kinase inhibitors (TKIs) in Ph + ALL, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best curative option. However, whether the prognostic significance of the identified LPCs phenotype to identify patients at high risk for relapse could retain in Ph + ALL after allo-HSCT, if any, is unknown. Aims: To investigate the prognostic significance of the candidate CD34 + CD38 - CD58 - LPCs in Ph + ALL subjects underwent allo-HSCT. Methods: A total of 80 consecutive adults (18-60 years) with Ph + ALL underwent allo-HSCT were eligible for the study at Peking University Institute of Hematology from January 1, 2009 to December 31, 2013. Imatinib was routinely administered in subjects pre- and post-HSCT as previously reported. A multi-parameter flow cytometry analysis of CD58-FITC/CD10-PE/CD19-APC-Cy7/CD34-PerCP/CD45-Vioblue/ CD38-APC on gated leukemia blasts of bone marrow was performed at diagnosis. Furthermore, minimal residual disease (MRD) was monitored by BCR/ABL transcripts in bone marrow samples at diagnosis, directly before transplantation, as well as serially at 1, 2, 3, 6, 9, 12,24,36,60 months post-HSCT and at relapse using real-time quantitative polymerase chain reaction. Cumulative incidences of relapse (CIR) and non-relapse mortality were calculated using the Kalbfleisch and Prentice method. Leukemia-free survival (LFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Factors at a level of P Results: On the basis of blasts phenotypes at diagnosis, subjects were stratified into CD34 + CD38 - CD58 - group (N=15) and other phenotype group (N=65). The demographic and clinical characteristics showed no significant difference between the two phenotype groups. Median follow-up was 25.5 mo (range, 6-65 mo) for all subjects and 33 mo (range, 6-65 mo) for survivors. During the MRD monitoring, significantly higher levels of BCR/ABL transcripts were detected in subjects in CD34 + CD38 - CD58 - group than persons in other phenotype group especially at 3 mo post-HSCT [0.12(0-152.4)% vs. 0(0-100)%, P =0.001]. Additionally, CD34 + CD38 - CD58 - LPCs phenotype directly correlated with higher 3-year CIR (63.2% [58.2-68.1%] vs . 5.3% [5.1-5.5%]; P vs . 78.7% [64.5-87.7%]; P =0.001) and OS (37.7% [12.6-63.2%] vs . 82.3% [68.5-90.4%]; P =0.0004). Multivariate analyses indicated that CD34 + CD38 - CD58 - LPCs phenotype at diagnosis and BCR-ABL reduction at 3 mo post-HSCT were independent risk factors for relapse, LFS and OS in adults with Ph + ALL underwent allo-HSCT. Summary/Conclusion: Our data suggest that a candidate CD34 + CD38 - CD58 - LPCs phenotype at diagnosis allows rapid identification of high-risk patients for relapse even after allo-HSCT. Risk-stratification post-HSCT therapy incorporating analysis of CD34 + CD38 - CD58 - LPCs phenotype at diagnosis promises to benefit the adults with Ph + ALL in the future. Acknowledgement: Supported by the National Natural Science Foundation of China (grant nos. 81370638&81230013), the Beijing Municipal Science and Technology Program (grant no. Z141100000214011), and Peking University People’s Hospital Research and Development Funds (grant no. RDB2012-23). Disclosures No relevant conflicts of interest to declare.

  • cd34 cd38 cd58 cells are leukemia propagating cells in philadelphia chromosome positive acute lymphoblastic leukemia
    Leukemia, 2014
    Co-Authors: Yuan Kong, Yingjun Chang, Yazhe Wang, Qian Jiang, Hao Jiang, Yazhen Qin, Yueyun Lai, Yong Liu, Caiwen Duan, Dengli Hong
    Abstract:

    CD34 + CD38 − CD58 − cells are leukemia-propagating cells in Philadelphia chromosome-positive acute lymphoblastic leukemia

Yazhen Qin - One of the best experts on this subject based on the ideXlab platform.

  • cd38 cd58 is an independent adverse prognostic factor in paediatric philadelphia chromosome negative b cell acute lymphoblastic leukaemia patients
    Leukemia Research, 2016
    Co-Authors: Leping Zhang, Yazhe Wang, Yazhen Qin, Honghu Zhu, Yueyun Lai, Yuan Kong, Xiaojun Huang, Yan Chang, Yanrong Liu
    Abstract:

    To explore new risk predictors for a high risk of relapse in Philadelphia chromosome negative (Ph-) B cell acute lymphoblastic leukaemia (B-ALL) patients, 196 paediatric Ph- B-ALL patients (≤ 18 years) were retrospectively analysed. We mainly focus on investigating the prognostic value of CD38 and CD58 expression in leukemic blasts in these patients by four colour flow cytometry. The CD38+ CD58- group (n=16) had a higher relapse rate, a shorter 3-year event-free survival (EFS) and overall survival (OS) than the CD38+ CD58+ group (n=157; 31.3% vs 10.2%, P=0.04; 52.4% vs 92.3%, P<0.01; 32.5% vs 91.0%, P=0.01); CD38+ CD58- was an independent adverse prognostic predictor for relapse (hazard ratio [HR], 0.203; 95%CI, 0.063-0.656; P=0.01), 3-year EFS (HR, 0.091; 95%CI, 0.023-0.355; P<0.01) and OS (HR, 0.102; 95%CI, 0.026-0.3971; P<0.01) in this cohort, as determined by Cox multivariate analysis. We identified, for the first time, a higher risk population of paediatric Ph- B-ALL patients with CD38+ CD58- who had a higher relapse risk and a shorter survival. Our results may allow better risk stratification and individualized treatment.

  • presence of cd34 cd38 cd58 leukemia propagating cells at diagnosis identifies patients at high risk of relapse with ph chromosome positive all after allo hematopoietic sct
    Bone Marrow Transplantation, 2015
    Co-Authors: Yuan Kong, Yingjun Chang, Qian Jiang, Hao Jiang, Yazhen Qin, Yong Liu, Yuanwei Sun, Yangyuan Wang, Huan Chen, Xiaojun Huang
    Abstract:

    Relapse of Ph chromosome-positive ALL (Ph+ALL) results from the persistence of leukemia-propagating cells (LPCs). In Ph+ALL, a xenograft assay recently determined that LPCs are enriched in the CD34+CD38−CD58− fraction. Therefore, the prognostic significance of LPCs in Ph+ALL subjects after allogeneic hematopoietic SCT (allo-HSCT) was investigated. A total of 80 consecutive adults with Ph+ALL who underwent allo-HSCT were eligible. A multi-parameter flow cytometry analysis examining CD58–FITC/CD10–PE/ CD19–APC–Cy7/CD34–PerCP/CD45–Vioblue/ CD38–APC on gated leukemia BM blasts was performed at diagnosis. Based on the original blast phenotypes, subjects were stratified into the CD34+CD38−CD58−group (N=15) and other phenotype group (N=65). During minimal residual disease monitoring, significantly higher levels of BCR/ABL transcripts were detected in subjects in the CD34+CD38−CD58− group than in other phenotype group, especially at 3 months post HSCT. In addition, CD34+CD38−CD58−LPCs are directly correlated with a higher 3-year cumulative incidence of relapse (CIR) and worse leukemia-free survival (LFS) and OS. Multivariate analyses indicated that presence of CD34+CD38−CD58− LPCs at diagnosis, and BCR–ABL reduction at 3 months post HSCT were independent risk factors for relapse, LFS and OS. Our data suggest that presence of CD34+CD38−CD58− LPCs at diagnosis allows rapid identification of high-risk patients for relapse after allo-HSCT.

  • cd34 cd38 cd58 leukemia propagating cells at diagnosis could identify patients at high risk for relapse in philadelphia chromosome positive acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation
    Blood, 2014
    Co-Authors: Yuan Kong, Yingjun Chang, Yanrong Liu, Qian Jiang, Hao Jiang, Yazhen Qin, Huan Chen, Yuqian Sun, Yu Wang, Xiaojun Huang
    Abstract:

    Background: Relapse of Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph + ALL) may result from the persistence of leukemia stem cells sometimes termed leukemia-propagating cells (LPCs). We recently found that Ph + ALL LPCs are enriched in the CD34 + CD38 - CD58 - fraction using anti-CD122-conditioned NOD/SCID xenograft assay by intra-bone marrow injection, which translating to adverse clinical outcomes (Kong Y, et al. Leukemia 2014. accepted). Despite the widespread use of abelson tyrosine kinase inhibitors (TKIs) in Ph + ALL, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best curative option. However, whether the prognostic significance of the identified LPCs phenotype to identify patients at high risk for relapse could retain in Ph + ALL after allo-HSCT, if any, is unknown. Aims: To investigate the prognostic significance of the candidate CD34 + CD38 - CD58 - LPCs in Ph + ALL subjects underwent allo-HSCT. Methods: A total of 80 consecutive adults (18-60 years) with Ph + ALL underwent allo-HSCT were eligible for the study at Peking University Institute of Hematology from January 1, 2009 to December 31, 2013. Imatinib was routinely administered in subjects pre- and post-HSCT as previously reported. A multi-parameter flow cytometry analysis of CD58-FITC/CD10-PE/CD19-APC-Cy7/CD34-PerCP/CD45-Vioblue/ CD38-APC on gated leukemia blasts of bone marrow was performed at diagnosis. Furthermore, minimal residual disease (MRD) was monitored by BCR/ABL transcripts in bone marrow samples at diagnosis, directly before transplantation, as well as serially at 1, 2, 3, 6, 9, 12,24,36,60 months post-HSCT and at relapse using real-time quantitative polymerase chain reaction. Cumulative incidences of relapse (CIR) and non-relapse mortality were calculated using the Kalbfleisch and Prentice method. Leukemia-free survival (LFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Factors at a level of P Results: On the basis of blasts phenotypes at diagnosis, subjects were stratified into CD34 + CD38 - CD58 - group (N=15) and other phenotype group (N=65). The demographic and clinical characteristics showed no significant difference between the two phenotype groups. Median follow-up was 25.5 mo (range, 6-65 mo) for all subjects and 33 mo (range, 6-65 mo) for survivors. During the MRD monitoring, significantly higher levels of BCR/ABL transcripts were detected in subjects in CD34 + CD38 - CD58 - group than persons in other phenotype group especially at 3 mo post-HSCT [0.12(0-152.4)% vs. 0(0-100)%, P =0.001]. Additionally, CD34 + CD38 - CD58 - LPCs phenotype directly correlated with higher 3-year CIR (63.2% [58.2-68.1%] vs . 5.3% [5.1-5.5%]; P vs . 78.7% [64.5-87.7%]; P =0.001) and OS (37.7% [12.6-63.2%] vs . 82.3% [68.5-90.4%]; P =0.0004). Multivariate analyses indicated that CD34 + CD38 - CD58 - LPCs phenotype at diagnosis and BCR-ABL reduction at 3 mo post-HSCT were independent risk factors for relapse, LFS and OS in adults with Ph + ALL underwent allo-HSCT. Summary/Conclusion: Our data suggest that a candidate CD34 + CD38 - CD58 - LPCs phenotype at diagnosis allows rapid identification of high-risk patients for relapse even after allo-HSCT. Risk-stratification post-HSCT therapy incorporating analysis of CD34 + CD38 - CD58 - LPCs phenotype at diagnosis promises to benefit the adults with Ph + ALL in the future. Acknowledgement: Supported by the National Natural Science Foundation of China (grant nos. 81370638&81230013), the Beijing Municipal Science and Technology Program (grant no. Z141100000214011), and Peking University People’s Hospital Research and Development Funds (grant no. RDB2012-23). Disclosures No relevant conflicts of interest to declare.

  • cd34 cd38 cd58 cells are leukemia propagating cells in philadelphia chromosome positive acute lymphoblastic leukemia
    Leukemia, 2014
    Co-Authors: Yuan Kong, Yingjun Chang, Yazhe Wang, Qian Jiang, Hao Jiang, Yazhen Qin, Yueyun Lai, Yong Liu, Caiwen Duan, Dengli Hong
    Abstract:

    CD34 + CD38 − CD58 − cells are leukemia-propagating cells in Philadelphia chromosome-positive acute lymphoblastic leukemia

  • cd34 cd38 cd58 candidate leukemia initiating cells are clinically relevant with the unfavorable prognosis in philadelphia chromosome positive acute lymphoblastic leukemia
    Blood, 2013
    Co-Authors: Yingjun Chang, Yanrong Liu, Yazhe Wang, Qian Jiang, Hao Jiang, Yazhen Qin, Jing Wang, Honghu Zhu, Yueyun Lai, Daihong Liu
    Abstract:

    ![Graphic][1] Background The prognosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) has been greatly improved in the modern era of imatinib. Nevertheless, relapse is still a major cause of treatment failure in human Ph+ALL. Leukemia-initiating cells (LICs) are presumed to be responsible for relapse in leukemia. Therefore, we conducted a study to identify the candidate LICs that are responsible for disease progression and its clinical significance in patients with Ph+ALL. Aims To investigate the leukemia-initiating and self-renewal capacities of CD34+CD38-CD58- cells and determine the prognostic significance of CD34+CD38-CD58- phenotype in patients with Ph+ALL treated in Peking University Institute of Hematology. Methods The leukemia-initiating potential and self-renewal capacity of the sorted CD34+CD38-CD58-, CD34+CD38-CD58+,CD34+CD38+CD58- and CD34+CD38+CD58+ compartments were investigated in vivo using sublethally irradiated and anti-mouse CD122 monoclonal antibody conditioned NOD/SCID mice by intra-bone marrow–injection. Furthermore, we prospectively analyzed whether the identified CD34+CD38-CD58- compartment at diagnosis correlates with minimal residual disease (MRD) after therapy and clinical outcomes in 63 adult patients (18-60 years) with de novo Ph+ALL. Results Xenotransplantation of the sorted CD34+CD38-CD58- cells led to a repopulation of human B-ALL in primary and secondary recipient mice, which were phenotypically and clonally derived from the original Ph+ALL patients analyzed by flow cytometry, as well as quantitative real-time RT-PCR and fluorescence in situ hybridization for leukemia-specific cytogenetic abnormalities. Furthermore, the candidate CD34+CD38-CD58- LICs phenotype at diagnosis (n=16) significantly correlated with a lower complete remission rate and higher MRD frequency monitored by BCR-ABL mRNA levels in BM of Ph+ALL patients. Additionally, it directly correlated with higher cumulative incidence of relapse (CIR, 60% ± 1.97% vs. 15.51% ± 0.30%, P =0.002) and unfavorable disease-free survival (DFS, 33.75%±12.64% vs. 71.31%±7.17%, P =0.009) at 3-year. The CD34+CD38-CD58- group exhibited a higher rate of BCR-ABL mutations conferring higher level imatinib resistance than the other group (43.75% vs. 17.02%, P =0.04). Multivariate analyses revealed that CD34+CD38-CD58- phenotype at diagnosis was an independent risk factor for relapse (HR=4.35, P =0.009) and DFS (HR=3.38, P =0.008) in adult Ph+ALL. Summary/Conclusion Both the xenotransplantation data as well as the clinical correlation studies show that CD34+CD38-CD58- compartment enrich for leukemia-initiating cells in adult Ph+ALL. CD34+CD38-CD58- phenotype at diagnosis independently correlates with an adverse prognosis, which promises to be an efficient tool for relapse prediction and risk-stratification treatment in adult Ph+ALL patients. Acknowledgments This work was supported by grants from National Natural Science Foundation of China (grants no. 30800483&81230013) and Beijing Municipal Science and Technology Program (grant no.Z111107067311070). Disclosures: No relevant conflicts of interest to declare. [1]: /embed/inline-graphic-2.gif

Dengli Hong - One of the best experts on this subject based on the ideXlab platform.

Yingjun Chang - One of the best experts on this subject based on the ideXlab platform.

  • presence of cd34 cd38 cd58 leukemia propagating cells at diagnosis identifies patients at high risk of relapse with ph chromosome positive all after allo hematopoietic sct
    Bone Marrow Transplantation, 2015
    Co-Authors: Yuan Kong, Yingjun Chang, Qian Jiang, Hao Jiang, Yazhen Qin, Yong Liu, Yuanwei Sun, Yangyuan Wang, Huan Chen, Xiaojun Huang
    Abstract:

    Relapse of Ph chromosome-positive ALL (Ph+ALL) results from the persistence of leukemia-propagating cells (LPCs). In Ph+ALL, a xenograft assay recently determined that LPCs are enriched in the CD34+CD38−CD58− fraction. Therefore, the prognostic significance of LPCs in Ph+ALL subjects after allogeneic hematopoietic SCT (allo-HSCT) was investigated. A total of 80 consecutive adults with Ph+ALL who underwent allo-HSCT were eligible. A multi-parameter flow cytometry analysis examining CD58–FITC/CD10–PE/ CD19–APC–Cy7/CD34–PerCP/CD45–Vioblue/ CD38–APC on gated leukemia BM blasts was performed at diagnosis. Based on the original blast phenotypes, subjects were stratified into the CD34+CD38−CD58−group (N=15) and other phenotype group (N=65). During minimal residual disease monitoring, significantly higher levels of BCR/ABL transcripts were detected in subjects in the CD34+CD38−CD58− group than in other phenotype group, especially at 3 months post HSCT. In addition, CD34+CD38−CD58−LPCs are directly correlated with a higher 3-year cumulative incidence of relapse (CIR) and worse leukemia-free survival (LFS) and OS. Multivariate analyses indicated that presence of CD34+CD38−CD58− LPCs at diagnosis, and BCR–ABL reduction at 3 months post HSCT were independent risk factors for relapse, LFS and OS. Our data suggest that presence of CD34+CD38−CD58− LPCs at diagnosis allows rapid identification of high-risk patients for relapse after allo-HSCT.

  • cd34 cd38 cd58 leukemia propagating cells at diagnosis could identify patients at high risk for relapse in philadelphia chromosome positive acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation
    Blood, 2014
    Co-Authors: Yuan Kong, Yingjun Chang, Yanrong Liu, Qian Jiang, Hao Jiang, Yazhen Qin, Huan Chen, Yuqian Sun, Yu Wang, Xiaojun Huang
    Abstract:

    Background: Relapse of Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph + ALL) may result from the persistence of leukemia stem cells sometimes termed leukemia-propagating cells (LPCs). We recently found that Ph + ALL LPCs are enriched in the CD34 + CD38 - CD58 - fraction using anti-CD122-conditioned NOD/SCID xenograft assay by intra-bone marrow injection, which translating to adverse clinical outcomes (Kong Y, et al. Leukemia 2014. accepted). Despite the widespread use of abelson tyrosine kinase inhibitors (TKIs) in Ph + ALL, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best curative option. However, whether the prognostic significance of the identified LPCs phenotype to identify patients at high risk for relapse could retain in Ph + ALL after allo-HSCT, if any, is unknown. Aims: To investigate the prognostic significance of the candidate CD34 + CD38 - CD58 - LPCs in Ph + ALL subjects underwent allo-HSCT. Methods: A total of 80 consecutive adults (18-60 years) with Ph + ALL underwent allo-HSCT were eligible for the study at Peking University Institute of Hematology from January 1, 2009 to December 31, 2013. Imatinib was routinely administered in subjects pre- and post-HSCT as previously reported. A multi-parameter flow cytometry analysis of CD58-FITC/CD10-PE/CD19-APC-Cy7/CD34-PerCP/CD45-Vioblue/ CD38-APC on gated leukemia blasts of bone marrow was performed at diagnosis. Furthermore, minimal residual disease (MRD) was monitored by BCR/ABL transcripts in bone marrow samples at diagnosis, directly before transplantation, as well as serially at 1, 2, 3, 6, 9, 12,24,36,60 months post-HSCT and at relapse using real-time quantitative polymerase chain reaction. Cumulative incidences of relapse (CIR) and non-relapse mortality were calculated using the Kalbfleisch and Prentice method. Leukemia-free survival (LFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Factors at a level of P Results: On the basis of blasts phenotypes at diagnosis, subjects were stratified into CD34 + CD38 - CD58 - group (N=15) and other phenotype group (N=65). The demographic and clinical characteristics showed no significant difference between the two phenotype groups. Median follow-up was 25.5 mo (range, 6-65 mo) for all subjects and 33 mo (range, 6-65 mo) for survivors. During the MRD monitoring, significantly higher levels of BCR/ABL transcripts were detected in subjects in CD34 + CD38 - CD58 - group than persons in other phenotype group especially at 3 mo post-HSCT [0.12(0-152.4)% vs. 0(0-100)%, P =0.001]. Additionally, CD34 + CD38 - CD58 - LPCs phenotype directly correlated with higher 3-year CIR (63.2% [58.2-68.1%] vs . 5.3% [5.1-5.5%]; P vs . 78.7% [64.5-87.7%]; P =0.001) and OS (37.7% [12.6-63.2%] vs . 82.3% [68.5-90.4%]; P =0.0004). Multivariate analyses indicated that CD34 + CD38 - CD58 - LPCs phenotype at diagnosis and BCR-ABL reduction at 3 mo post-HSCT were independent risk factors for relapse, LFS and OS in adults with Ph + ALL underwent allo-HSCT. Summary/Conclusion: Our data suggest that a candidate CD34 + CD38 - CD58 - LPCs phenotype at diagnosis allows rapid identification of high-risk patients for relapse even after allo-HSCT. Risk-stratification post-HSCT therapy incorporating analysis of CD34 + CD38 - CD58 - LPCs phenotype at diagnosis promises to benefit the adults with Ph + ALL in the future. Acknowledgement: Supported by the National Natural Science Foundation of China (grant nos. 81370638&81230013), the Beijing Municipal Science and Technology Program (grant no. Z141100000214011), and Peking University People’s Hospital Research and Development Funds (grant no. RDB2012-23). Disclosures No relevant conflicts of interest to declare.

  • cd34 cd38 cd58 cells are leukemia propagating cells in philadelphia chromosome positive acute lymphoblastic leukemia
    Leukemia, 2014
    Co-Authors: Yuan Kong, Yingjun Chang, Yazhe Wang, Qian Jiang, Hao Jiang, Yazhen Qin, Yueyun Lai, Yong Liu, Caiwen Duan, Dengli Hong
    Abstract:

    CD34 + CD38 − CD58 − cells are leukemia-propagating cells in Philadelphia chromosome-positive acute lymphoblastic leukemia

  • cd34 cd38 cd58 candidate leukemia initiating cells are clinically relevant with the unfavorable prognosis in philadelphia chromosome positive acute lymphoblastic leukemia
    Blood, 2013
    Co-Authors: Yingjun Chang, Yanrong Liu, Yazhe Wang, Qian Jiang, Hao Jiang, Yazhen Qin, Jing Wang, Honghu Zhu, Yueyun Lai, Daihong Liu
    Abstract:

    ![Graphic][1] Background The prognosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) has been greatly improved in the modern era of imatinib. Nevertheless, relapse is still a major cause of treatment failure in human Ph+ALL. Leukemia-initiating cells (LICs) are presumed to be responsible for relapse in leukemia. Therefore, we conducted a study to identify the candidate LICs that are responsible for disease progression and its clinical significance in patients with Ph+ALL. Aims To investigate the leukemia-initiating and self-renewal capacities of CD34+CD38-CD58- cells and determine the prognostic significance of CD34+CD38-CD58- phenotype in patients with Ph+ALL treated in Peking University Institute of Hematology. Methods The leukemia-initiating potential and self-renewal capacity of the sorted CD34+CD38-CD58-, CD34+CD38-CD58+,CD34+CD38+CD58- and CD34+CD38+CD58+ compartments were investigated in vivo using sublethally irradiated and anti-mouse CD122 monoclonal antibody conditioned NOD/SCID mice by intra-bone marrow–injection. Furthermore, we prospectively analyzed whether the identified CD34+CD38-CD58- compartment at diagnosis correlates with minimal residual disease (MRD) after therapy and clinical outcomes in 63 adult patients (18-60 years) with de novo Ph+ALL. Results Xenotransplantation of the sorted CD34+CD38-CD58- cells led to a repopulation of human B-ALL in primary and secondary recipient mice, which were phenotypically and clonally derived from the original Ph+ALL patients analyzed by flow cytometry, as well as quantitative real-time RT-PCR and fluorescence in situ hybridization for leukemia-specific cytogenetic abnormalities. Furthermore, the candidate CD34+CD38-CD58- LICs phenotype at diagnosis (n=16) significantly correlated with a lower complete remission rate and higher MRD frequency monitored by BCR-ABL mRNA levels in BM of Ph+ALL patients. Additionally, it directly correlated with higher cumulative incidence of relapse (CIR, 60% ± 1.97% vs. 15.51% ± 0.30%, P =0.002) and unfavorable disease-free survival (DFS, 33.75%±12.64% vs. 71.31%±7.17%, P =0.009) at 3-year. The CD34+CD38-CD58- group exhibited a higher rate of BCR-ABL mutations conferring higher level imatinib resistance than the other group (43.75% vs. 17.02%, P =0.04). Multivariate analyses revealed that CD34+CD38-CD58- phenotype at diagnosis was an independent risk factor for relapse (HR=4.35, P =0.009) and DFS (HR=3.38, P =0.008) in adult Ph+ALL. Summary/Conclusion Both the xenotransplantation data as well as the clinical correlation studies show that CD34+CD38-CD58- compartment enrich for leukemia-initiating cells in adult Ph+ALL. CD34+CD38-CD58- phenotype at diagnosis independently correlates with an adverse prognosis, which promises to be an efficient tool for relapse prediction and risk-stratification treatment in adult Ph+ALL patients. Acknowledgments This work was supported by grants from National Natural Science Foundation of China (grants no. 30800483&81230013) and Beijing Municipal Science and Technology Program (grant no.Z111107067311070). Disclosures: No relevant conflicts of interest to declare. [1]: /embed/inline-graphic-2.gif

Hao Jiang - One of the best experts on this subject based on the ideXlab platform.

  • presence of cd34 cd38 cd58 leukemia propagating cells at diagnosis identifies patients at high risk of relapse with ph chromosome positive all after allo hematopoietic sct
    Bone Marrow Transplantation, 2015
    Co-Authors: Yuan Kong, Yingjun Chang, Qian Jiang, Hao Jiang, Yazhen Qin, Yong Liu, Yuanwei Sun, Yangyuan Wang, Huan Chen, Xiaojun Huang
    Abstract:

    Relapse of Ph chromosome-positive ALL (Ph+ALL) results from the persistence of leukemia-propagating cells (LPCs). In Ph+ALL, a xenograft assay recently determined that LPCs are enriched in the CD34+CD38−CD58− fraction. Therefore, the prognostic significance of LPCs in Ph+ALL subjects after allogeneic hematopoietic SCT (allo-HSCT) was investigated. A total of 80 consecutive adults with Ph+ALL who underwent allo-HSCT were eligible. A multi-parameter flow cytometry analysis examining CD58–FITC/CD10–PE/ CD19–APC–Cy7/CD34–PerCP/CD45–Vioblue/ CD38–APC on gated leukemia BM blasts was performed at diagnosis. Based on the original blast phenotypes, subjects were stratified into the CD34+CD38−CD58−group (N=15) and other phenotype group (N=65). During minimal residual disease monitoring, significantly higher levels of BCR/ABL transcripts were detected in subjects in the CD34+CD38−CD58− group than in other phenotype group, especially at 3 months post HSCT. In addition, CD34+CD38−CD58−LPCs are directly correlated with a higher 3-year cumulative incidence of relapse (CIR) and worse leukemia-free survival (LFS) and OS. Multivariate analyses indicated that presence of CD34+CD38−CD58− LPCs at diagnosis, and BCR–ABL reduction at 3 months post HSCT were independent risk factors for relapse, LFS and OS. Our data suggest that presence of CD34+CD38−CD58− LPCs at diagnosis allows rapid identification of high-risk patients for relapse after allo-HSCT.

  • cd34 cd38 cd58 leukemia propagating cells at diagnosis could identify patients at high risk for relapse in philadelphia chromosome positive acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation
    Blood, 2014
    Co-Authors: Yuan Kong, Yingjun Chang, Yanrong Liu, Qian Jiang, Hao Jiang, Yazhen Qin, Huan Chen, Yuqian Sun, Yu Wang, Xiaojun Huang
    Abstract:

    Background: Relapse of Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph + ALL) may result from the persistence of leukemia stem cells sometimes termed leukemia-propagating cells (LPCs). We recently found that Ph + ALL LPCs are enriched in the CD34 + CD38 - CD58 - fraction using anti-CD122-conditioned NOD/SCID xenograft assay by intra-bone marrow injection, which translating to adverse clinical outcomes (Kong Y, et al. Leukemia 2014. accepted). Despite the widespread use of abelson tyrosine kinase inhibitors (TKIs) in Ph + ALL, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best curative option. However, whether the prognostic significance of the identified LPCs phenotype to identify patients at high risk for relapse could retain in Ph + ALL after allo-HSCT, if any, is unknown. Aims: To investigate the prognostic significance of the candidate CD34 + CD38 - CD58 - LPCs in Ph + ALL subjects underwent allo-HSCT. Methods: A total of 80 consecutive adults (18-60 years) with Ph + ALL underwent allo-HSCT were eligible for the study at Peking University Institute of Hematology from January 1, 2009 to December 31, 2013. Imatinib was routinely administered in subjects pre- and post-HSCT as previously reported. A multi-parameter flow cytometry analysis of CD58-FITC/CD10-PE/CD19-APC-Cy7/CD34-PerCP/CD45-Vioblue/ CD38-APC on gated leukemia blasts of bone marrow was performed at diagnosis. Furthermore, minimal residual disease (MRD) was monitored by BCR/ABL transcripts in bone marrow samples at diagnosis, directly before transplantation, as well as serially at 1, 2, 3, 6, 9, 12,24,36,60 months post-HSCT and at relapse using real-time quantitative polymerase chain reaction. Cumulative incidences of relapse (CIR) and non-relapse mortality were calculated using the Kalbfleisch and Prentice method. Leukemia-free survival (LFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Factors at a level of P Results: On the basis of blasts phenotypes at diagnosis, subjects were stratified into CD34 + CD38 - CD58 - group (N=15) and other phenotype group (N=65). The demographic and clinical characteristics showed no significant difference between the two phenotype groups. Median follow-up was 25.5 mo (range, 6-65 mo) for all subjects and 33 mo (range, 6-65 mo) for survivors. During the MRD monitoring, significantly higher levels of BCR/ABL transcripts were detected in subjects in CD34 + CD38 - CD58 - group than persons in other phenotype group especially at 3 mo post-HSCT [0.12(0-152.4)% vs. 0(0-100)%, P =0.001]. Additionally, CD34 + CD38 - CD58 - LPCs phenotype directly correlated with higher 3-year CIR (63.2% [58.2-68.1%] vs . 5.3% [5.1-5.5%]; P vs . 78.7% [64.5-87.7%]; P =0.001) and OS (37.7% [12.6-63.2%] vs . 82.3% [68.5-90.4%]; P =0.0004). Multivariate analyses indicated that CD34 + CD38 - CD58 - LPCs phenotype at diagnosis and BCR-ABL reduction at 3 mo post-HSCT were independent risk factors for relapse, LFS and OS in adults with Ph + ALL underwent allo-HSCT. Summary/Conclusion: Our data suggest that a candidate CD34 + CD38 - CD58 - LPCs phenotype at diagnosis allows rapid identification of high-risk patients for relapse even after allo-HSCT. Risk-stratification post-HSCT therapy incorporating analysis of CD34 + CD38 - CD58 - LPCs phenotype at diagnosis promises to benefit the adults with Ph + ALL in the future. Acknowledgement: Supported by the National Natural Science Foundation of China (grant nos. 81370638&81230013), the Beijing Municipal Science and Technology Program (grant no. Z141100000214011), and Peking University People’s Hospital Research and Development Funds (grant no. RDB2012-23). Disclosures No relevant conflicts of interest to declare.

  • cd34 cd38 cd58 cells are leukemia propagating cells in philadelphia chromosome positive acute lymphoblastic leukemia
    Leukemia, 2014
    Co-Authors: Yuan Kong, Yingjun Chang, Yazhe Wang, Qian Jiang, Hao Jiang, Yazhen Qin, Yueyun Lai, Yong Liu, Caiwen Duan, Dengli Hong
    Abstract:

    CD34 + CD38 − CD58 − cells are leukemia-propagating cells in Philadelphia chromosome-positive acute lymphoblastic leukemia

  • cd34 cd38 cd58 candidate leukemia initiating cells are clinically relevant with the unfavorable prognosis in philadelphia chromosome positive acute lymphoblastic leukemia
    Blood, 2013
    Co-Authors: Yingjun Chang, Yanrong Liu, Yazhe Wang, Qian Jiang, Hao Jiang, Yazhen Qin, Jing Wang, Honghu Zhu, Yueyun Lai, Daihong Liu
    Abstract:

    ![Graphic][1] Background The prognosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) has been greatly improved in the modern era of imatinib. Nevertheless, relapse is still a major cause of treatment failure in human Ph+ALL. Leukemia-initiating cells (LICs) are presumed to be responsible for relapse in leukemia. Therefore, we conducted a study to identify the candidate LICs that are responsible for disease progression and its clinical significance in patients with Ph+ALL. Aims To investigate the leukemia-initiating and self-renewal capacities of CD34+CD38-CD58- cells and determine the prognostic significance of CD34+CD38-CD58- phenotype in patients with Ph+ALL treated in Peking University Institute of Hematology. Methods The leukemia-initiating potential and self-renewal capacity of the sorted CD34+CD38-CD58-, CD34+CD38-CD58+,CD34+CD38+CD58- and CD34+CD38+CD58+ compartments were investigated in vivo using sublethally irradiated and anti-mouse CD122 monoclonal antibody conditioned NOD/SCID mice by intra-bone marrow–injection. Furthermore, we prospectively analyzed whether the identified CD34+CD38-CD58- compartment at diagnosis correlates with minimal residual disease (MRD) after therapy and clinical outcomes in 63 adult patients (18-60 years) with de novo Ph+ALL. Results Xenotransplantation of the sorted CD34+CD38-CD58- cells led to a repopulation of human B-ALL in primary and secondary recipient mice, which were phenotypically and clonally derived from the original Ph+ALL patients analyzed by flow cytometry, as well as quantitative real-time RT-PCR and fluorescence in situ hybridization for leukemia-specific cytogenetic abnormalities. Furthermore, the candidate CD34+CD38-CD58- LICs phenotype at diagnosis (n=16) significantly correlated with a lower complete remission rate and higher MRD frequency monitored by BCR-ABL mRNA levels in BM of Ph+ALL patients. Additionally, it directly correlated with higher cumulative incidence of relapse (CIR, 60% ± 1.97% vs. 15.51% ± 0.30%, P =0.002) and unfavorable disease-free survival (DFS, 33.75%±12.64% vs. 71.31%±7.17%, P =0.009) at 3-year. The CD34+CD38-CD58- group exhibited a higher rate of BCR-ABL mutations conferring higher level imatinib resistance than the other group (43.75% vs. 17.02%, P =0.04). Multivariate analyses revealed that CD34+CD38-CD58- phenotype at diagnosis was an independent risk factor for relapse (HR=4.35, P =0.009) and DFS (HR=3.38, P =0.008) in adult Ph+ALL. Summary/Conclusion Both the xenotransplantation data as well as the clinical correlation studies show that CD34+CD38-CD58- compartment enrich for leukemia-initiating cells in adult Ph+ALL. CD34+CD38-CD58- phenotype at diagnosis independently correlates with an adverse prognosis, which promises to be an efficient tool for relapse prediction and risk-stratification treatment in adult Ph+ALL patients. Acknowledgments This work was supported by grants from National Natural Science Foundation of China (grants no. 30800483&81230013) and Beijing Municipal Science and Technology Program (grant no.Z111107067311070). Disclosures: No relevant conflicts of interest to declare. [1]: /embed/inline-graphic-2.gif