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ACUTE MYELOID LEUKEMIA

The gene mutation landscape of acute myeloid leukemia cell lines and its exemplar use to study the BCOR tumor suppressor

Leukemia volume 37, pages 473–477 (2023)Cite this article

Subjects

Human cell lines derived from acute myeloid leukemia (AML) patients with recurrent cytogenetic abnormalities proved instrumental to understand the mechanisms of leukemogenesis and to test the activity of new drugs. For example, the NB4 cell line carrying the t(15;17) typical of acute promyelocytic leukemia allowed to clarify the molecular mechanisms of transformation and to demonstrate the differentiation effect of all-trans-retinoic acid and arsenic trioxide.

About half of AMLs have normal karyotype and are driven by recurrent mutations [1] that, in the most recent genomic classifications [2, 3], allow risk stratification of AML patients according to the European LeukemiaNet (ELN) [4]. For example, NPM1 mutations in the absence of FLT3-ITD associate with favorable prognosis while mutations of TP53 or genes encoding chromatin and/or splicing regulators (e.g., ASXL1, BCOR, SRSF2) predict a poor prognosis [2,3,4].

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Fig. 1: Gene mutation landscape of human AML cell lines.
Fig. 2: BCOR reconstitution in AML cells with BCOR-disruptive mutations inhibits proliferation, induces differentiation, and downregulates HOXA gene expression.

Data availability

BAM files will be available at the European Nucleotide Archive under the accession number PRJEB56663.

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Acknowledgements

BF acknowledges the support from Associazione Italiana Ricerca sul Cancro (AIRC; Investigator Grant 23604).

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Author notes

  1. These authors contributed equally: Valentina Pettirossi, Alessandra Venanzi.

  2. These authors jointly supervised this work: Brunangelo Falini, Enrico Tiacci.

Authors and Affiliations

  1. Institute of Hematology and Center for Hemato-Oncology Research, Department of Medicine and Surgery, University and Hospital of Perugia, Perugia, Italy

    Valentina Pettirossi, Alessandra Venanzi, Ariele Spanhol-Rosseto, Gianluca Schiavoni, Alessia Santi, Luisa Tasselli, Marta Naccari, Valentina Pensato, Alessandra Pucciarini, Maria Paola Martelli, Brunangelo Falini & Enrico Tiacci

  2. Faculty of Life Sciences, Technical University of Braunschweig, Braunschweig, Germany

    Hans Drexler

Authors
  1. Valentina Pettirossi
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Contributions

VP and AV designed research, performed experiments, analyzed data, and wrote the manuscript; AR performed experiments; GS, AS, LT, MN, VPen, AP, and MPM analyzed data; HD contributed vital reagents; BF conceived the study and edited the manuscript; ET conceived and directed the study, designed research, analyzed data and wrote the manuscript.

Corresponding author

Correspondence to Enrico Tiacci.

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Pettirossi, V., Venanzi, A., Spanhol-Rosseto, A. et al. The gene mutation landscape of acute myeloid leukemia cell lines and its exemplar use to study the BCOR tumor suppressor. Leukemia 37, 473–477 (2023). https://doi.org/10.1038/s41375-022-01788-7

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