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

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 obs...

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Veröffentlicht in:	Stem cell research 2016-09, Vol.17 (2), p.235-237
Hauptverfasser:	Telliam, G., Féraud, O., Griscelli, F., Opolon, P., Divers, D., Bennaceur-Griscelli, A., Turhan, A.G.
Format:	Artikel
Sprache:	eng
Schlagworte:	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
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Zusammenfassung:	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.
ISSN:	1873-5061 1876-7753
DOI:	10.1016/j.scr.2016.08.001