By Pier Paolo Pandolfi (Editor), Peter K. Vogt (Editor)
Over 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 features in transcriptional regulate, constructing mouse types and culminating within the improvement of specified treatment.
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Extra info for Acute Promyelocytic Leukemia: Molecular Genetics, Mouse Models and Targeted Therapy (Current Topics in Microbiology and Immunology 313)
Blood 85:1083–1094 46 M. J. McConnell · J. D. Licht 46. Licht JD, Shaknovich R, English MA, Melnick A, Li JY, Reddy JC, Dong S, Chen SJ, Zelent A, Waxman S (1996) Reduced and altered DNA-binding and transcriptional properties of the PLZF-retinoic acid receptor-alpha chimera generated in t(11;17)associated acute promyelocytic leukemia. Oncogene 12:323–336 47. Lin RJ, Nagy L, Inoue S, Shao W, Miller WH Jr, Evans RM (1998) Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature 391:811–814 48.
J. McConnell · J. D. edu Abstract The PLZF gene is one of ﬁve partners fused to the retinoic acid receptor αin acute promyelocytic leukemia. PLZF encodes a DNA-binding transcriptional repressor and the PLZF-RARα fusion protein like other RARα fusions can inhibit the genetic program mediated by the wild tpe retinoic acid receptor. However an increasing body of literature indicates an important role for the PLZF gene in growth control and development. This information suggests that loss of PLZF function might also contribute to leukemogenesis.
The FAZF protein also has a BTB domain, and three Kruppel-like C2 H2 zinc ﬁngers highly homologous to the ﬁnal three DNA-binding zinc ﬁngers of PLZF. It can heterodimerize with PLZF, and can bind the same DNA sequences as PLZF in vitro . FAZF is found in a pattern of nuclear foci similar to the PLZF speckles, and forced expression in a U937 cell had the same suppression of growth and induction of apoptosis as PLZF . The phenotype of the FAZF knockout mouse demonstrates that while FAZF has a distinct role in other tissues, its expression and function overlap with PLZF in the CD34+ progenitor cell .
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)