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Gatekeeper pathways and cellular background in the pathogenesis and therapy of AML

Abstract

Acute myelogenous leukemia (AML) is characterized by the accumulation of immature cells due to disturbed differentiation and proliferation of the myeloid lineage. Genetic alterations affecting transcription factors and receptor tyrosine kinases have been identified in AML and causally linked to the disease. The goal of this review is to address the role of the different genetic alterations in self-renewal and proliferation and to discuss the cellular background in which these events occur during the pathogenesis of AML. Data from AML samples, clinical studies and mouse models for AML will be used to support the different theories regarding the leukemogenesis of AML. Finally, this review wants to highlight the implication of these findings for the therapy of AML.

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Acknowledgements

I thank Dr Carol Stocking for her tremendous help and support writing this review and the members of both labs for helpful discussion and critical reading of the manuscript. I am very grateful to Dr JA McCubrey who gave me the opportunity to write this review. Thanks to Dr C Klug and Dr L Castilla for sharing data before publication. I apologize to all colleagues whose excellent works have not been cited in this review due to space limitations.

The Heinrich-Pette-Institute belongs to the Wilhelm Leibniz Gesellschaft and is supported by the Freie und Hansestadt Hamburg. Jörg Cammenga and Carol Stocking were supported by the DFG and the José Carreras Leukemia Foundation.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu).

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Supplementary Figure 1

Expression and activity of the promoters used in different mouse models of AML (excluding MLL and HOX). (JPG 231 kb)

Supplementary Table 1

Mouse models for AML listed by subtype (excluding translocations involving the MLL and HOX genes). Abbreviations: TG, transgenic; BM, bone marrow; RCR, replication competent retrovirus; ND, not determined; ENU, N-ethyl-N-nitrosourea; ATRA, all-trans retinoic acid; ES cells, embryonic stem cells; APL, acute promyelocytic leukemia; CML-L, CML-like; MPD, myeloproliferative diseases; MDS, myelodysplastic syndromes. (XLS 26 kb)

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Cammenga, J. Gatekeeper pathways and cellular background in the pathogenesis and therapy of AML. Leukemia 19, 1719–1728 (2005). https://doi.org/10.1038/sj.leu.2403894

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