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Sci Rep. 2021 Oct 27;11(1):21145. doi: 10.1038/s41598-021-00623-w.

Divergent leukaemia subclones as cellular models for testing vulnerabilities associated with gains in chromosomes 7, 8 or 18.

Scientific reports

Michael Maher, Jeannine Diesch, Marguerite-Marie Le Pannérer, Marta Cabezón, Mar Mallo, Sara Vergara, Aleix Méndez López, Alba Mesa Tudel, Francesc Solé, Marc Sorigue, Lurdes Zamora, Isabel Granada, Marcus Buschbeck

Affiliations

  1. Cancer and Leukaemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), 08916, Badalona, Spain.
  2. Program for Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), Campus Can Ruti, 08916, Badalona, Spain.
  3. Department of Hematology Laboratory, ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute (IJC), 08916, Badalona, Spain.
  4. Microarrays Unit, Josep Carreras Leukaemia Research Institute (IJC), 08916, Badalona, Spain.
  5. MDS Group, Josep Carreras Leukaemia Research Institute (IJC), 08916, Badalona, Spain.
  6. Cancer and Leukaemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), 08916, Badalona, Spain. [email protected].
  7. Program for Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), Campus Can Ruti, 08916, Badalona, Spain. [email protected].

PMID: 34707142 PMCID: PMC8551338 DOI: 10.1038/s41598-021-00623-w

Abstract

Haematopoietic malignancies are frequently characterized by karyotypic abnormalities. The development of targeted drugs has been pioneered with compounds against gene products of fusion genes caused by chromosomal translocations. While polysomies are equally frequent as translocations, for many of them we are lacking therapeutic approaches aimed at synthetic lethality. Here, we report two new cell lines, named MBU-7 and MBU-8, that differ in complete trisomy of chromosome18, a partial trisomy of chromosome 7 and a tetrasomy of the p-arm of chromosome 8, but otherwise share the same mutational pattern and complex karyotype. Both cell lines are divergent clones of U-937 cells and have the morphology and immunoprofile of monocytic cells. The distinct karyotypic differences between MBU-7 and MBU-8 are associated with a difference in the specific response to nucleoside analogues. Taken together, we propose the MBU-7 and MBU-8 cell lines described here as suitable in vitro models for screening and testing vulnerabilities that are associated with the disease-relevant polysomies of chromosome 7, 8 and 18.

© 2021. The Author(s).

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