Efficient RNA interference in patients' acute lymphoblastic leukemia cells amplified as xenografts in mice

Signaling studies in cell lines are hampered by non-physiological alterations obtained in vitro. Physiologic primary tumor cells from patients with leukemia require passaging through immune-compromised mice for amplification. The aim was to enable molecular work in patients' ALL cells by establishing siRNA transfection into cells amplified in mice. We established delivering siRNA into these cells without affecting cell viability. Knockdown of single or multiple genes reduced constitutive or induced protein expression accompanied by marked signaling alterations. Our novel technique allows using patient-derived tumor cells instead of cell lines for signaling studies in leukemia.

• Publication year

  2012

• Venue

  Cell Communication and Signaling

• Publication date

  2012-03-26

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/1478-811X-10-8PMID 22448764PMCID 3349556
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Optimized anti-tumor effects of anthracyclines plus Vinca alkaloids using a novel, mechanism-based application schedule.

  2011cited by this paper
• Xenografts of highly resistant leukemia recapitulate the clonal composition of the leukemogenic compartment.

  2011cited by this paper
• Cytotoxic drug-induced, p53-mediated upregulation of caspase-8 in tumor cells

  2008cited by this paper
• Humanized mice in translational biomedical research

  2007cited by this paper
• Targeting of gene expression by siRNA in CML primary cells

  2007cited by this paper
• Efficient nucleofection of primary human B cells and B-CLL cells induces apoptosis, which depends on the microenvironment and on the structure of transfected nucleic acids

  2007cited by this paper
• Cancer cell lines as genetic models of their parent histology: analyses based on array comparative genomic hybridization.

  2007cited by this paper
• Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database

  2007cited by this paper
• p53 and disease: when the guardian angel fails

  2006cited by this paper
• BCR-ABL activity is critical for the immunogenicity of chronic myelogenous leukemia cells.

  2006cited by this paper
• Assessment of tumor characteristic gene expression in cell lines using a tissue similarity index (TSI).

  2005cited by this paper
• Preclinical testing of antileukemic drugs using an in vivo model of systemic disease.

  2005cited by this paper
• Tumor necrosis factor-related apoptosis-inducing ligand-mediated proliferation of tumor cells with receptor-proximal apoptosis defects.

  2005influential reference
• TP53 in hematological cancer: Low incidence of mutations with significant clinical relevance

  2003cited by this paper
• TRAIL induced survival and proliferation in cancer cells resistant towards TRAIL-induced apoptosis mediated by NF-κB

  2003cited by this paper
• The nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of childhood acute lymphoblastic leukemia reveals intrinsic differences in biologic characteristics at diagnosis and relapse.

  2002cited by this paper
• CHILDHOOD ALL BLASTS RETAIN PHENOTYPIC AND GENOTYPIC CHARACTERISTICS UPON LONG-TERM SERIAL PASSAGE IN NOD/SCID MICE

  2000cited by this paper
• A model of human acute lymphoblastic leukemia in immune-deficient SCID mice.

  1989cited by this paper

• RNAi-Mediated Screen of Primary AML Cells Nominates MDM4 as a Therapeutic Target in NK-AML with DNMT3A Mutations

  2022cites this paper
• Cell cycle-arrested tumor cells exhibit increased sensitivity towards TRAIL-induced apoptosis

  2013influential citation
• Impact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling

  2013cites this paper
• Activation of DNA damage response by antitumor therapy counteracts the activity of vinca alkaloids.

  2013cites this paper
• NOXA as critical mediator for drug combinations in polychemotherapy

  2012cites this paper
• Adipocytes Enhance the Proliferation of Human Leiomyoma Cells Via TNF-α Proinflammatory Cytokine

  2011cites this paper