The role of p73 in hematological malignancies.
The P73 gene is a homologue of the P53 tumor suppressor. Owing to its structural similarity with p53, p73 was originally considered to have tumor suppressor function. However, the discovery of N-terminal truncated isoforms with oncogenic properties showed a 'two in one' structure of its product, p73 protein. The full-length variants are strong inducers of apoptosis, whereas the truncated isoforms inhibit proapoptotic activity of p53 and the full-length p73. Thus, p73 is involved in the regulation of cell cycle, cell death and development. Moreover, it plays a role in carcinogenesis and controls tumor sensitivity to treatment. p73 is commonly expressed in tumor cells in hematological malignancies. Overexpression of p73 protein and aberrant expression of its particular isoforms, with very low frequency of P73 hypermethylation or mutations, were found in malignant myeloproliferations, including acute myeloblastic leukemia. In contrast, hypermethylation and subsequent inactivation of the P73 gene are the most common findings in malignant lymphoproliferative disorders, especially acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphomas. Assessment of P73 methylation may provide important prognostic information, as was confirmed in patients with ALL. This review summarizes some aspects of p73 biology with particular reference to its possible pathogenetic role and prognostic significance in hematological malignancies.
Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland.
A
A
Pluta
U
U
Nyman
B
B
Joseph
T
T
Robak
B
B
Zhivotovsky
P
P
Smolewski
D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins