Transposon mutagenesis reveals fludarabine-resistance mechanisms in chronic lymphocytic leukemia

Purpose:To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired resistance to fludarabine-based chemotherapy represents a major challenge for long-term disease control. Methods: We employed piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, to identify genes that confer resistance to fludarabine in a human CLL cell line. Results: RNA-seq profiling of fludarabine-resistant cells suggested deregulated MAPK signaling as involved in mediating drug resistance in CLL. Overall design: To address if the fludarabine-resistant HG3 cells were transcriptionally different at a global level compared to their parental cells, we performed RNA-sequencing of three pairs of HG3 pools

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Pandzic T, Larsson J, He L, Kundu S, Ban K, Akhtar-Ali M, Hellström AR, Schuh A, Clifford R, Blakemore SJ, Strefford JC, Baumann T, Lopez-Guillermo A, Campo E, Ljungström V, Mansouri L, Rosenquist R, Sjöblom T, Hellström M