CRISPR genome editing of murine hematopoietic stem cells to create Npm1-Alk causes ALK+ lymphoma after transplantation

Blood Adv. 2019 Jun 25;3(12):1788-1794. doi: 10.1182/bloodadvances.2018025247.

Abstract

  1. CRISPR/Cas9 genomic editing of wild-type hematopoietic stem cells generates Npm1-Alk, leading to ALK+ large-cell lymphomas in recipients.

  2. CD30+ postthymic T-cell lymphomas are polyclonal but transplantable to secondary recipients with long latency.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Anaplastic Lymphoma Kinase / metabolism
  • Animals
  • Bone Marrow / virology
  • Cell Culture Techniques / methods
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Fetal Tissue Transplantation / methods
  • Fetus / surgery
  • Gene Editing / methods*
  • Hematopoietic Stem Cell Transplantation / methods
  • Hematopoietic Stem Cell Transplantation / veterinary
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Liver / surgery
  • Lymphoma, T-Cell / genetics*
  • Lymphoma, T-Cell / surgery
  • Lymphoma, T-Cell / veterinary
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Nuclear Proteins / metabolism
  • Nucleophosmin
  • Oncogene Proteins, Fusion / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Retroviridae Infections / complications
  • Stem Cells / virology
  • Young Adult

Substances

  • NPM1 protein, human
  • Npm1 protein, mouse
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Nucleophosmin
  • Alk protein, mouse
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases