CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-07-27

AUTHORS

Elad Jacoby, Sang M. Nguyen, Thomas J. Fountaine, Kathryn Welp, Berkley Gryder, Haiying Qin, Yinmeng Yang, Christopher D. Chien, Alix E. Seif, Haiyan Lei, Young K. Song, Javed Khan, Daniel W. Lee, Crystal L. Mackall, Rebecca A. Gardner, Michael C. Jensen, Jack F. Shern, Terry J. Fry

ABSTRACT

Adoptive immunotherapy using chimeric antigen receptor (CAR) expressing T cells targeting the CD19 B lineage receptor has demonstrated marked success in relapsed pre-B-cell acute lymphoblastic leukaemia (ALL). Persisting CAR-T cells generate sustained pressure against CD19 that may drive unique mechanisms of resistance. Pre-B ALL originates from a committed pre-B cell or an earlier progenitor, with potential to reprogram into other hematopoietic lineages. Here we report changes in lineage markers including myeloid conversion in patients following CD19 CAR therapy. Using murine ALL models we study the long-term effects of CD19 CAR-T cells and demonstrate partial or complete lineage switch as a consistent mechanism of CAR resistance depending on the underlying genetic oncogenic driver. Deletion of Pax5 or Ebf1 recapitulates lineage reprogramming occurring during CD19 CAR pressure. Our findings establish lineage switch as a mechanism of CAR resistance exposing inherent plasticity in genetic subtypes of pre-B-cell ALL. More... »

PAGES

12320

References to SciGraph publications

  • 2014-03. CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage in LEUKEMIA
  • 2014-02. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia in NATURE
  • 2007-09. Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors in NATURE
  • 2010-07. A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate in NATURE IMMUNOLOGY
  • 1999-10. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5 in NATURE
  • 1999-10. Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors in NATURE
  • 2005-03. CD 19 function in central and peripheral B-cell development in IMMUNOLOGIC RESEARCH
  • 2013-04. Cell of origin determines clinically relevant subtypes of MLL-rearranged AML in LEUKEMIA
  • 2003-09. Origins of chromosome translocations in childhood leukaemia in NATURE REVIEWS CANCER
  • 2013-08. Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells in NATURE IMMUNOLOGY
  • 2013-05. MLL–AF9-mediated immortalization of human hematopoietic cells along different lineages changes during ontogeny in LEUKEMIA
  • 2015-04. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias in NATURE GENETICS
  • 2014-12. Immune-based therapies for childhood cancer in NATURE REVIEWS CLINICAL ONCOLOGY
  • 2013-06. In focus: MLL-rearranged leukemia in LEUKEMIA
  • 2007-05. Pax5: the guardian of B cell identity and function in NATURE IMMUNOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms12320

    DOI

    http://dx.doi.org/10.1038/ncomms12320

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1019545875

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27460500


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