By Pier Paolo Pandolfi (Editor), Peter K. Vogt (Editor)
During the last 10 years, paintings on acute promyelocytic leukemia (APL) has turn into the paradigm of translational examine that all started with the invention of a recurrent chromosomal translocation, through the identity of the genes and proteins concerned, discovering their molecular capabilities in transcriptional keep watch over, constructing mouse types and culminating within the improvement of detailed treatment.
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Extra resources for Acute Promyelocytic Leukemia: Molecular Genetics, Mouse Models and Targeted Therapy (Current Topics in Microbiology and Immunology 313)
This gene was cloned and named the promyelocytic leukemia zinc ﬁnger (PLZF) gene [7, 8], also known as ZNF145 and more recently as ZBTB16. Since then, 17 cases of APL with a fusion between the PLZF and RARα genes have been described [11, 21, 22, 38, 45] representing less than 1% of cases of APL. Initial data suggested that unlike typical APL with the PML-RARα rearrangement, these patients had a poor prognosis, were resistant to treatment with all-trans retinoic acid (ATRA) and generally did not respond to chemotherapy .
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. The resistant phenotype of t(11;17) APL can be explained in part by a gain-of-function mutation of RARα in which the protein becomes a constitutive repressor of key genes required for normal myeloid maturation. However, closer study of PLZF has revealed additional layers of complexity in the development of APL.
Overexpression of PLZF in melanoma lines caused a decrease in proliferation, blocked invasion and foci formation in semi-solid media, and enhanced melanocytic differentiation. Additionally, melanoma cells expressing PLZF had reduced growth in nude mice compared to parental cells, implying PLZF has tumor suppressor activity that was lost in this malignancy . PLZF has traditionally been thought of as a nuclear protein, as beﬁts a transcription factor, and in fact it is localized to the nucleus [46, 67] in the distinct nuclear speckled pattern described earlier.