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Annals of Hematology

, Volume 97, Issue 5, pp 799–811 | Cite as

Leukemia-propagating cells demonstrate distinctive gene expression profiles compared with other cell fractions from patients with de novo Philadelphia chromosome-positive ALL

  • Hong-Yan Zhao
  • Yang Song
  • Xie-Na Cao
  • Ya-Zhen Qin
  • Yue-Yun Lai
  • Hao Jiang
  • Qian Jiang
  • Xiao-Jun Huang
  • Yuan Kong
Original Article
  • 143 Downloads

Abstract

Relapse remains one of the major obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) even after allogeneic hematopoietic stem cell transplantation. The persistence of leukemia-propagating cells (LPCs) may lead to the recurrence of Ph+ALL. Using a xenograft assay, LPCs enrichment in the CD34+CD38CD58 fraction in Ph+ALL was recently identified. A further cohort study indicated that the LPCs phenotype at diagnosis was an independent risk factor for relapse of Ph+ALL. However, little is known about the potential molecular mechanism of LPCs-mediated relapse. Therefore, the gene expression profiles of the sorted LPCs and other cell fractions from patients with de novo Ph+ALL were investigated using RNA sequencing (RNA-Seq). Most of the differentially expressed genes between the LPCs and other cell fractions were related to the regulation of the cell cycle and metabolism, as identified by the gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Consistent with the RNA-Seq results, the mRNA levels of cell cycle-related genes, such as cyclin-dependent kinase 4, were significantly lower in the LPCs fraction than in other cell fractions. Moreover, the proportion of quiescent cells in LPCs was significantly higher than in other cell fractions. In summary, distinctive gene expression profiles and clusters, which were mostly related to the regulation of the cell cycle and metabolism, were demonstrated between LPCs and other cell fractions from patients with de novo Ph+ALL. Therefore, it would be beneficial to develop novel LPCs-based therapeutic strategies for Ph+ALL patients.

Keywords

Acute lymphoblastic leukemia Leukemia-propagating cells Gene expression profiles Metabolism 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant nos. 81570127&81370638&81530046), Milstein Medical Asian American Partnership (MMAAP) Foundation, the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81621001), Beijing Municipal Science and Technology Program (Z151100004015164), and the Science and Technology Project of Guangdong Province of China (2016B030230003). American Journal Experts (www.journalexperts.com) provided editorial assistance to the authors during the preparation of the manuscript. The authors thank all of the core facilities at Peking University Institute of Hematology for sample collection.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Peking University People’s Hospital (reference number: 2015PHB214-01). Informed consent was obtained from all patients and donors before entry into the study in accordance with the Declaration of Helsinki.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Hong-Yan Zhao
    • 1
  • Yang Song
    • 1
    • 2
  • Xie-Na Cao
    • 1
  • Ya-Zhen Qin
    • 1
  • Yue-Yun Lai
    • 1
  • Hao Jiang
    • 1
  • Qian Jiang
    • 1
  • Xiao-Jun Huang
    • 1
    • 2
  • Yuan Kong
    • 1
  1. 1.Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of HematologyPeking UniversityBeijingChina
  2. 2.Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijingChina

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