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Genome-wide identification of microRNA signatures associated with stem/progenitor cells in Philadelphia chromosome-positive acute lymphoblastic leukemia

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Abstract

Acute lymphoblastic leukemia (ALL) is a malignant transformation with uncontrolled proliferation of lymphoid precursor cells within bone marrow including a dismal prognosis after relapse. Survival of a population of quiescent leukemia stem cells (LSCs, also termed leukemia-initiating cells (LICs)) after treatment is one of the relapse reasons in Ph+ ALL patient. MicroRNAs (miRNAs) are known as highly conserved 19–24 nucleotides non-protein-coding small RNAs that regulate the expression of human genes. miRNAs are often involved in the tuning of hematopoiesis. Therefore, the deregulation of miRNA expression and function in hematopoietic cells can cause cancer and promote its progression. This is the first comprehensive analysis of miRNA expression differences between CD34+CD38− LSCs and CD34+CD38+ leukemic progenitors (LPs) from the same Ph+ B-ALL bone marrow samples using high-throughput sequencing technologies. We identified multiple differentially expressed miRNAs including hsa-miR-3143, hsa-miR-6503-3p, hsa-miR-744-3p, hsa-miR-1226-3p, hsa-miR-10a-5p, hsa-miR-4658 and hsa-miR-493-3p related to LSC and LP populations which have regulatory functions in stem-cell associated biological processes. The deregulation of these miRNAs could affect leukemogenesis, clonogenic and stemness capacities in these subpopulations of Ph+ B-ALL. Therefore, identification of these LSC associated miRNAs may improve the diagnosis and management of B-ALL. These findings may also lead to future strategies to eliminate the presence of resistant LSCs, either by induction of apoptosis or by sensitizing these cells to chemotherapy.

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Acknowledgements

The authors wish to thank the Research Vice Chancellor of Mashhad University of Medical Sciences (MUMS), Mashhad, Iran for financial support of this study.

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Authors and Affiliations

  1. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Ehsan Valiollahi & Javad Behravan

  2. Josep Carreras Research Institute (IJC), ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain

    Josep Maria Ribera & Eulàlia Genescà

  3. School of Pharmacy, University of Waterloo, 200 University Ave, Waterloo, N2L 3G1, Canada

    Javad Behravan

  4. Theraphage Inc, Waterloo, ON, Canada

    Javad Behravan

  5. Mediphage Bioceuticals, Inc, 661 University Avenue, Suite 1300, MaRS Centre, West Tower, Toronto, M5G0B7, Canada

    Javad Behravan

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  1. Ehsan Valiollahi
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Correspondence to Eulàlia Genescà or Javad Behravan.

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Valiollahi, E., Ribera, J.M., Genescà, E. et al. Genome-wide identification of microRNA signatures associated with stem/progenitor cells in Philadelphia chromosome-positive acute lymphoblastic leukemia. Mol Biol Rep 46, 1295–1306 (2019). https://doi.org/10.1007/s11033-019-04600-5

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