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Acute Leukemia

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 volume 50, pages 348–353 (2015)Cite this article

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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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant no. 81370638 & 81230013), the Beijing Municipal Science and Technology Program, the National Clinical Priority Specialty and the Peking University People’s Hospital Research and Development Funds (grant no. RDB2012-23). American Journal Experts (www.journalexperts.com) offered editorial assistance to the authors during the preparation of this manuscript. We thank all of the core facilities at the Peking University Institute of Hematology for sample collection.

Author Contributions

X-JH designed the study and supervised the analyses and manuscript preparation. YK performed the research, analyzed and interpreted the data, performed statistical analyses and wrote the manuscript. All other authors participated in the collection of patient data. All the authors agreed to submit the final manuscript.

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  1. Y Kong and L-P Xu: These authors contributed equally to this work.

Authors and Affiliations

  1. Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

    Y Kong, L-P Xu, Y-R Liu, Y-Z Qin, Y-Q Sun, Y Wang, H Jiang, Q Jiang, H Chen, Y-J Chang & X-J Huang

  2. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China

    X-J Huang

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Kong, Y., Xu, LP., Liu, YR. et al. 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 Transplant 50, 348–353 (2015). https://doi.org/10.1038/bmt.2014.274

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