title: Alterations of mitochondrial biogenesis in chronic lymphocytic leukemia cells with loss of p53.
abstract: Deletion of chromosome 17p with a loss of p53 is an unfavorable cytogenetic change in chronic lymphocytic leukemia (CLL) with poor clinical outcome. Since p53 affects mitochondrial function and integrity, we examined possible mitochondrial changes in CLL mice with TCL1-Tg/p53-/-and TCL1-Tg/p53+/+genotypes and in primary leukemia cells from CLL patients with or without 17p-deletion. Although the expression of mitochondrial COX1, ND2, and ND6 decreased in p53-/-CLL cells, there was an increase in mitochondrial biogenesis as evidenced by higher mitochondrial mass and mtDNA copy number associated with an elevated expression of TFAM and PGC-1α. Surprisingly, the overall mitochondrial respiratory activity and maximum reserved capacity increased in p53-/-CLL cells. Our study suggests that leukemia cells lacking p53 seem able to maintain respiratory function by compensatory increase in mitochondrial biogenesis.
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Ogasawara
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jinyun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Helene
authors.initials: H
authors.lastname: Pelicano
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors.forename: Naima
authors.initials: N
authors.lastname: Hammoudi
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA. Electronic address: phuang@mdanderson.org.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
mesh_terms: D000818:Animals; D019069:Cell Respiration; D002872:Chromosome Deletion; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D001678:Organelle Biogenesis; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency*
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: Chronic lymphocytic leukemia; Mitochondrial biogenesis; p53