Acute Promyelocytic Leukemia: Molecular Genetics, Mouse by Pier Paolo Pandolfi (Editor), Peter K. Vogt (Editor)

By Pier Paolo Pandolfi (Editor), Peter K. Vogt (Editor)

Over the last 10 years, paintings on acute promyelocytic leukemia (APL) has develop into the paradigm of translational examine that all started with the invention of a recurrent chromosomal translocation, by way of the id of the genes and proteins concerned, discovering their molecular services in transcriptional keep an eye on, developing mouse versions and culminating within the improvement  of designated treatment.

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Additional resources for Acute Promyelocytic Leukemia: Molecular Genetics, Mouse Models and Targeted Therapy (Current Topics in Microbiology and Immunology 313)

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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.

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. Science 278:1059–1064 52. Martin PJ, Delmotte MH, Formstecher P, Lefebvre P (2003) PLZF is a negative regulator of retinoic acid receptor transcriptional activity. Nucl Recept 1:6 53.

Only in this in vivo context can hypotheses about pathogenesis be definitively proved or refuted. Furthermore, animal models of APL are equally important for assessing ideas regarding the value of novel therapies. As we learn more about APL, added questions are raised. Among the areas that animal models will be used for in the coming years are: 1. Developing a better understanding of the cells from which relapses arise in APL and other AMLs. ) 2. Identifying the critical transcriptional targets repressed by X-RARα proteins.

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