Efficient transduction of healthy and malignant plasma cells by lentiviral vectors pseudotyped with measles virus glycoproteins

Schoenhals, Matthieu; Frecha, Cecilia; Bruyer, Angélique; Caraux, Anouk; Jl, Veyrune; Jourdan, Michel; Moreaux, Jérôme; Cosset, François‐Loïc; Verhoeyen, Els; Klein, Bernard

doi:10.1038/leu.2012.36

Cited by 9 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To confirm that RECQ1 is also required for the survival of primary MMCs from patients, BM samples containing malignant MMCs were transduced 45 , 46 with shRECQ1 lentiviruses and primary MM cells were cultured with their BM environment and recombinant IL-6 as described. 17 RECQ1 depletion significantly reduced the median number of viable myeloma cells by 56% ( P =0.004; N =7) compared to scramble shRNA ( Figure 3b ).…”

Section: Resultsmentioning

confidence: 99%

RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma

et al. 2017

Self Cite

View full text Add to dashboard Cite

Multiple myeloma (MM) is a plasma cell cancer with poor survival, characterized by the expansion of multiple myeloma cells (MMCs) in the bone marrow. Using a microarray-based genome-wide screen for genes responding to DNA methyltransferases (DNMT) inhibition in MM cells, we identified RECQ1 among the most downregulated genes. RecQ helicases are DNA unwinding enzymes involved in the maintenance of chromosome stability. Here we show that RECQ1 is significantly overexpressed in MMCs compared to normal plasma cells and that increased RECQ1 expression is associated with poor prognosis in three independent cohorts of patients. Interestingly, RECQ1 knockdown inhibits cells growth and induces apoptosis in MMCs. Moreover, RECQ1 depletion promotes the development of DNA double-strand breaks, as evidenced by the formation of 53BP1 foci and the phosphorylation of ataxia-telangiectasia mutated (ATM) and histone variant H2A.X (H2AX). In contrast, RECQ1 overexpression protects MMCs from melphalan and bortezomib cytotoxicity. RECQ1 interacts with PARP1 in MMCs exposed to treatment and RECQ1 depletion sensitizes MMCs to poly(ADP-ribose) polymerase (PARP) inhibitor. DNMT inhibitor treatment results in RECQ1 downregulation through miR-203 deregulation in MMC. Altogether, these data suggest that association of DNA damaging agents and/or PARP inhibitors with DNMT inhibitors may represent a therapeutic approach in patients with high RECQ1 expression associated with a poor prognosis.

show abstract

Section: Resultsmentioning

confidence: 99%

RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Finally, the retroviridae family is known to be exceptionally amendable to pseudotyping54. Various studies have shown increased specificity of gene transfer with vectors pseudotyped with RD114 glycoprotein to various stem cells5556, pseudotyping with measles virus glycoprotein to target plasma cells57, or display of antibodies or DARPins to transduce hematopoietic progenitor cells or cancer cells5058.…”

Section: Discussionmentioning

confidence: 99%

Non-integrating gamma-retroviral vectors as a versatile tool for transient zinc-finger nuclease delivery

Bobis‐Wozowicz

Galla

Alzubi

et al. 2014

Sci Rep

View full text Add to dashboard Cite

Designer nucleases, like zinc-finger nucleases (ZFNs), represent valuable tools for targeted genome editing. Here, we took advantage of the gamma-retroviral life cycle and produced vectors to transfer ZFNs in the form of protein, mRNA and episomal DNA. Transfer efficacy and ZFN activity were assessed in quantitative proof-of-concept experiments in a human cell line and in mouse embryonic stem cells. We demonstrate that retrovirus-mediated protein transfer (RPT), retrovirus-mediated mRNA transfer (RMT), and retrovirus-mediated episome transfer (RET) represent powerful methodologies for transient protein delivery or protein expression. Furthermore, we describe complementary strategies to augment ZFN activity after gamma-retroviral transduction, including serial transduction, proteasome inhibition, and hypothermia. Depending on vector dose and target cell type, gene disruption frequencies of up to 15% were achieved with RPT and RMT, and >50% gene knockout after RET. In summary, non-integrating gamma-retroviral vectors represent a versatile tool to transiently deliver ZFNs to human and mouse cells.

show abstract

“…LLPCs) could help to understand better their function. Of note, it is now feasible to force or repress the expression of a given gene in these PCs using measles envelop pseudotyped lentiviral delivery 56. The same holds true for drugs used to treat patients with MM, in particular to identify if these drugs could target a specific PB or…”

mentioning

confidence: 99%

IL-6 supports the generation of human long-lived plasma cells in combination with either APRIL or stromal cell-soluble factors

Jourdan

Cren

Naeije³

et al. 2014

Leukemia

Self Cite

110

131

View full text Add to dashboard Cite

The recent understanding of plasma cell (PC) biology has been obtained from murine models mainly. The current concept is that plasmablasts home to the BM and further differentiate into long-lived PCs (LLPCs). These LLPCs survive for months in contact with a complex niche comprising stromal cells (SCs) and hematopoietic cells both producing recruitment and survival factors. Using a multi-step culture system, we show here the possibility to differentiate human memory B cells into LLPCs surviving for at least 4 months in vitro and producing immunoglobulins continuously. A remarkable feature is that IL-6 is mandatory to generate LLPCs in vitro together with either APRIL or soluble factors produced by SCs, unrelated to APRIL/BAFF, SDF-1, or IGF-1. These LLPCs are out of the cell cycle, express highly PC transcription factors and surface markers. This model shows a remarkable robustness of human LLPCs, which can survive and produce highly immunoglobulins for months in vitro without contact with niche cells, providing the presence of a minimal cocktail of growth factors and nutrients. This model should be useful to understand further normal PC biology and its deregulation in premalignant or malignant PC disorders.

show abstract

Efficient transduction of healthy and malignant plasma cells by lentiviral vectors pseudotyped with measles virus glycoproteins

Cited by 9 publications

References 31 publications

RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma

RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma

Non-integrating gamma-retroviral vectors as a versatile tool for transient zinc-finger nuclease delivery

IL-6 supports the generation of human long-lived plasma cells in combination with either APRIL or stromal cell-soluble factors

Contact Info

Product

Resources

About