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

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 t...

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Detalles Bibliográficos
Autores: Maher, Michael|||0000-0002-4956-7185, Diesch, Jeannine|||0000-0002-4667-3468, Le Pannérer, Marguerite Marie|||0000-0002-5779-8805, Cabezón, Marta|||0000-0001-5122-7481, Mallo, Maria del Mar|||0000-0001-7741-498X, Vergara, Sara, Méndez López, Aleix, Mesa Tudel, Alba|||0000-0002-8377-7573, Sole, F.|||0000-0002-3251-2161, Sorigue, Marc|||0000-0002-0587-591X, Zamora, Lurdes|||0000-0003-1713-7110, Granada, Isabel|||0000-0002-4275-0104, Buschbeck, Marcus|||0000-0002-3218-4567
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:270563
Acceso en línea:https://ddd.uab.cat/record/270563
https://dx.doi.org/urn:doi:10.1038/s41598-021-00623-w
Access Level:acceso abierto
Palabra clave:Biomarkers, Tumor
Cell Line, Tumor
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 7
Chromosomes, Human, Pair 8
Humans
Leukemia, Myeloid, Acute
Tetrasomy
Trisomy
Descripción
Sumario: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.