TY - JOUR AU - Srdana Grgurevic, AU - Patricia Montilla-Perez, AU - Alice Bradbury, AU - Julia Gilhodes, AU - Sophie Queille, AU - Sandrine Pelofy, AU - Aurélien Bancaud, AU - Thomas Filleron, AU - Loïc Ysebaert, AU - Christian Récher, AU - Guy Laurent, AU - Jean-Jacques Fournié, AU - Christophe Cazaux, AU - Anne Quillet-Mary, AU - Jean-Sébastien Hoffmann, PY - 2018/06/03 Y2 - 2024/03/28 TI - DNA polymerase ν gene expression influences fludarabine resistance in chronic lymphocytic leukemia independently of p53 status JF - Haematologica JA - haematol VL - 103 IS - 6 SE - Articles DO - 10.3324/haematol.2017.174243 UR - https://haematologica.org/article/view/8479 SP - 1038-1046 AB - Alteration in the DNA replication, repair or recombination processes is a highly relevant mechanism of genomic instability. Despite genomic aberrations manifested in hematologic malignancies, such a defect as a source of biomarkers has been underexplored. Here, we investigated the prognostic value of expression of 82 genes involved in DNA replication-repair-recombination in a series of 99 patients with chronic lymphocytic leukemia without detectable 17p deletion or TP53 mutation. We found that expression of the POLN gene, encoding the specialized DNA polymerase ν (Pol ν) correlates with time to relapse after first-line therapy with fludarabine. Moreover, we found that POLN was the only gene up-regulated in primary patients’ lymphocytes when exposed in vitro to proliferative and pro-survival stimuli. By using two cell lines that were sequentially established from the same patient during the course of the disease and Pol ν knockout mouse embryonic fibroblasts, we reveal that high relative POLN expression is important for DNA synthesis and cell survival upon fludarabine treatment. These findings suggest that Pol ν could influence therapeutic resistance in chronic lymphocytic leukemia. (Patients’ samples were obtained from the CLL 2007 FMP clinical trial registered at: clinicaltrials.gov identifer: 00564512). ER -