Cancer and neoplasms

The acidic stretch and the C-terminal nuclear export signal motif of NPM1 mutant: are they druggable in AML?

Posted on by yun
22
Sep

NPM1-mutated acute myeloid leukemia (AML) is the most common genetic type of adult AML (about 30%-35% of cases) [1] and, due to its distinctive molecular and clinico-pathological features [2, 3], is recognized as a new leukemia entity in the 2022 ICC [4] and WHO fifth edition [5] classifications of myeloid neoplasms. Two distinguishing biological characteristics of NPM1-mutated AML which are of potential relevance for its molecular targeted therapy are: (i) the high expression of HOX genes such as HOXA9 and MEIS1; [6] and (ii) the aberrant nuclear export of NPM1 in the cytoplasm of leukemic cells [1]. Upregulation of HOX genes and abnormal traffic of NPM1 can be targeted using menin inhibitors and XPO1 (CRM1) inhibitors, respectively [2, 3].

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Fig. 1: Application of the Abd technology to the NPM1 mutant.

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Acknowledgements

This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC IG 2019 number 23604) and the European Research Council (Advanced Grant 2016 number 740230).

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Authors and Affiliations

  1. Institute of Hematology and Center for Hemato-Oncological research (CREO), University of Perugia and Santa Maria della Misericordia Hospital, Perugia, Italy

    Brunangelo Falini

  2. Centre for Cancer Biomarkers (CCBIO), Department of Clinical Science, University of Bergen, Bergen, Norway

    Bjorn T. Gjertsen & Vibeke Andresen

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BF coordinated the study and all authors contributed to wrote the manuscript.

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Conflict-of-interest disclosure: BF holds a patent on NPM1 mutants (number 102004901256449). The remaining authors declare no competing financial interests.

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Falini, B., Gjertsen, B.T. & Andresen, V. The acidic stretch and the C-terminal nuclear export signal motif of NPM1 mutant: are they druggable in AML?.
Leukemia (2023). https://doi.org/10.1038/s41375-023-02037-1

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  • Received: 26 July 2023

  • Revised: 06 September 2023

  • Accepted: 12 September 2023

  • Published: 22 September 2023

  • DOI: https://doi.org/10.1038/s41375-023-02037-1

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