Generation of an induced pluripotent stem cell line from a patient with chronic myeloid leukemia (CML) resistant to targeted therapies

Stem Cell Res. 2016 Sep;17(2):235-237. doi: 10.1016/j.scr.2016.08.001. Epub 2016 Aug 4.

Abstract

Chronic myeloid leukemia (CML) is a clonal malignancy initiated by the occurrence of a t (9;22) translocation, generating Ph1 chromosome and BCR-ABL oncogene in a primitive hematopoietic stem cell (HSC). The resistance of HSC to targeted therapies using tyrosine kinase inhibitors remains a major obstacle towards the cure. We have generated an iPSC line from a patient with CML using leukemic CD34+ cells cryopreserved at diagnosis. Ph1+ CML cells were reprogrammed by non-integrative viral transduction. These iPSCs harboured Ph1 chromosome and expressed pluripotency hallmarks as well as BCR-ABL. Teratoma assays revealed normal differentiation after injection in immunodeficient mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Antigens, CD34 / metabolism
  • Cell Differentiation
  • Cellular Reprogramming*
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Induced Pluripotent Stem Cells / transplantation
  • Karyotype
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Leukocytes, Mononuclear / cytology*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Mice
  • Mice, Inbred NOD
  • Teratoma / metabolism
  • Teratoma / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Antigens, CD34
  • Transcription Factors
  • Fusion Proteins, bcr-abl