By Pier Paolo Pandolfi (Editor), Peter K. Vogt (Editor)
During the last 10 years, paintings on acute promyelocytic leukemia (APL) has develop into the paradigm of translational examine that started with the invention of a recurrent chromosomal translocation, through the id of the genes and proteins concerned, discovering their molecular features in transcriptional regulate, constructing mouse versions and culminating within the improvement of specific remedy.
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Additional info for Acute Promyelocytic Leukemia: Molecular Genetics, Mouse Models and Targeted Therapy (Current Topics in Microbiology and Immunology 313)
Nature 391:811–814 48. Reference deleted in proof 49. Lin W, Lai CH, Tang CJ, Huang CJ, Tang TK (1999) Identiﬁcation and gene structure of a novel human PLZF-related transcription factor gene, TZFP. Biochem Biophys Res Commun 264:789–795 50. Long JJ, Leresche A, Kriwacki RW, Gottesfeld JM (1998) Repression of TFIIH transcriptional activity and TFIIH-associated cdk7 kinase activity at mitosis. Mol Cell Biol 18:1467–1476 51. Look AT (1997) Oncogenic transcription factors in the human acute leukemias.
The less common splice variants AS-II, AS-III, and AS-IV have a restricted pattern of tissue-speciﬁc expression. These variants maintain the open reading frame, but encode an N-terminally truncated PLZF protein . The PLZF protein is a DNA-binding zinc ﬁnger transcription factor of 673 amino acids that generally acts as a transcriptional repressor . The Nterminal 118 amino acids constitute the PLZF BTB (broad-complex, tramtrack, bric a brac) domain, also known as a POZ (pox virus and zinc ﬁnger) domain, which is essential for transcriptional repression .
This effect of PLZF might be relevant to APL. Loss of one allele of PLZF might lead to deregulation of the stem cell; a decision in favor of proliferation may be made rather than quiescence. In this regard we note that while PLZF is a growth suppressor, the RARα-PLZF oncoprotein, which can bind to many of the same DNA-binding sites of wildtype PLZF, activates genes that PLZF represses and induces a myeloproliferative disease in mice. 42 M. J. McConnell · J. D. Licht Summary The study of the t(11;17)-associated forms of APL and the PLZF protein has served as a paradigm for the role that aberrant transcriptional repression plays in hematological malignancy.
Acute Promyelocytic Leukemia: Molecular Genetics, Mouse Models and Targeted Therapy (Current Topics in Microbiology and Immunology 313) by Pier Paolo Pandolfi (Editor), Peter K. Vogt (Editor)