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 begun with the invention of a recurrent chromosomal translocation, via the identity of the genes and proteins concerned, discovering their molecular services in transcriptional keep watch over, constructing mouse types and culminating within the improvement of designated 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)
Licht PLZF-null mice do not exhibit an obvious hematopoietic phenotype, nor do they develop leukemia or other tumors. However, this does not rule out a role for PLZF in hematopoiesis. A second PLZF-like gene exists, which is expressed in a similar pattern during differentiation of hematopoietic progenitor cells. 1, suggesting that it arose by duplication of the PLZF-MLL locus at 11q23. 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.
This all suggests that FAZF might compensate for the lack of PLZF during hematopoietic development. PLZF is expressed in a number of tissues outside the hematopoietic system. During development of the central nervous system PLZF is expressed in a segmental pattern in hindbrain , indicating possible regulation of transcription of the Hoxb2 gene. A PLZF-binding site was found in the Hoxb2 5 ﬂanking region and PLZF could repress the Hoxb2 promoter in cotransfection assays [36, 37]. PLZF expression is also notable in the limb buds where Hox genes have an essential role.
The transcription factor GATA2, which is important for hematopoietic progenitor cell commitment , also interacts with PLZF, leading to a block in GATA2-mediated transactivation . The effect of these interactions on PLZF repression activity has not been described, but downregulation of the action of other factors is a signiﬁcant way in which PLZF could modulate hematopoietic development. Interestingly, both a physical interaction and functional crosstalk between RARα and GATA2 has been described in myeloid differentiation , suggesting that regulation of this process by PLZF would have a signiﬁcant role in normal and malignant hematopoiesis.
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)