3R gene expression in chronic lymphocytic leukemia reveals insight into disease evolution

Grgurević, Srđana; Berquet, Laure; Quillet‐Mary, Anne; Laurent, Guy; Récher, Christian; Ysebaert, Loïc; Cazaux, Christophe; Hoffmann, Jean-Sébastien

doi:10.1038/bcj.2016.39

Cited by 2 publications

(2 citation statements)

References 15 publications

(17 reference statements)

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“…The patient’s baseline characteristics are summarized in Table 1 . Unsupervised clustering on 3R gene expression values confirmed, as previously published, 18 clear underlying differences between samples from healthy donors and CLL lymphocytes ( Figure 1A ) and showed a significantly higher expression in CLL of POLN , the gene encoding for the specialized DNA polymerase ν ( Figure 1B ), as compared to most of the 3R genes, including other specialized DNA polymerases or genes involved in double-stranded break repair ( Online Supplementary Figure S1 ). Next, we performed a cross-analysis on the gene expression information obtained and the patients’ clinical data.…”

Section: Resultssupporting

confidence: 86%

DNA polymerase ν gene expression influences fludarabine resistance in chronic lymphocytic leukemia independently of p53 status

Grgurević¹,

Montilla‐Perez²,

Bradbury³

et al. 2018

Haematologica

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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).

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Section: Resultssupporting

confidence: 86%

DNA polymerase ν gene expression influences fludarabine resistance in chronic lymphocytic leukemia independently of p53 status

Grgurević¹,

Montilla‐Perez²,

Bradbury³

et al. 2018

Haematologica

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show abstract

“…46 Furthermore, CLL genome is characterized by deregulated expression of genes involved in DNA replication, repair and recombination. 47 Taking these observations into account, we surmised that targeting dividing leukemic cells may represent a therapeutic strategy in CLL and therefore hypothesized that CHK1 kinase, which is essential for DNA replication and recombination-based repair, can be a suitable target.…”

Section: Discussionmentioning

confidence: 99%

Novel CHK1 inhibitor MU380 exhibits significant single-agent activity in TP53-mutated chronic lymphocytic leukemia cells

et al. 2019

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3R gene expression in chronic lymphocytic leukemia reveals insight into disease evolution

Cited by 2 publications

References 15 publications

DNA polymerase ν gene expression influences fludarabine resistance in chronic lymphocytic leukemia independently of p53 status

DNA polymerase ν gene expression influences fludarabine resistance in chronic lymphocytic leukemia independently of p53 status

Novel CHK1 inhibitor MU380 exhibits significant single-agent activity in TP53-mutated chronic lymphocytic leukemia cells

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