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 begun with the invention of a recurrent chromosomal translocation, by means of 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 designated remedy.
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Extra info for Acute Promyelocytic Leukemia: Molecular Genetics, Mouse Models and Targeted Therapy (Current Topics in Microbiology and Immunology 313)
9 Therapy, Conclusions 1. Animal models of leukemia can be used to assess the potential role of the immune system in controlling malignant cell growth, and to examine strategies to boost the immune response to AML. The use of mouse models in which the leukemic oncoproteins are themselves expressed from murine genes may enhance the relevance of such studies to future human clinical investigation. 2. APL models have been used in preclinical studies to assess the potential value of new AML therapies.
C. Kogan Minucci S, Monestiroli S, Giavara S, Ronzoni S, Marchesi F, Insinga A, Diverio D, Gasparini P, Capillo M, Colombo E, Matteucci C, Contegno F, Lo-Coco F, Scanziani E, Gobbi A, Pelicci PG (2002) PML-RAR induces promyelocytic leukemias with high efﬁciency following retroviral gene transfer into puriﬁed murine hematopoietic progenitors. Blood 100:2989–2995 Molica S, Mannella A, Dattilo A, Levato D, Iuliano F, Peta A, Consarino C, Magro S (1996) Differential expression of BCL-2 oncoprotein and Fas antigen on normal peripheral blood and leukemic bone marrow cells.
Cotylenin A is a plant growth regulator that is able to induce differentiation of human myeloid leukemia cell lines and primary AML blasts. The xenograft 24 S. C. Kogan mouse model of APL was used to show that cotylenin A can prolong survival in mice engrafted with the RA-sensitive NB4 cell line, or a RA-resistant version of NB4 (Honma et al. 2003). The possible utility of cotylenin A (or a derivative) as an antileukemic agent in humans is not yet clear. Another observation of uncertain clinical beneﬁt is that hypoxia can facilitate differentiation of myeloid leukemic cells in vitro.
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)