BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemia

• Published in: The Journal of experimental medicine Vol. 208; no. 11; pp. 2163 - 2174
• Main Authors: Hurtz, Christian, Hatzi, Katerina, Cerchietti, Leandro, Braig, Melanie, Park, Eugene, Kim, Yong-mi, Herzog, Sebastian, Ramezani-Rad, Parham, Jumaa, Hassan, Müller, Martin C., Hofmann, Wolf-Karsten, Hochhaus, Andreas, Ye, B. Hilda, Agarwal, Anupriya, Druker, Brian J., Shah, Neil P., Melnick, Ari M., Müschen, Markus
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 24.10.2011
• Subjects: Animals; Antigens, CD34 - metabolism; Benzamides; Brief Definitive Report; Cell Survival; Disease Models, Animal; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Forkhead Transcription Factors - metabolism; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - physiopathology; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Neoplasm Transplantation; Neoplastic Stem Cells - physiology; Piperazines - therapeutic use; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-6; Pyrimidines - therapeutic use; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism

Chronic myeloid leukemia (CML) is induced by the oncogenic BCR-ABL1 tyrosine kinase and can be effectively treated for many years with tyrosine kinase inhibitors (TKIs). However, unless CML patients receive life-long TKI treatment, leukemia will eventually recur; this is attributed to the failure of...