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Título
The CRISPR/Cas9 system efficiently reverts the tumorigenic ability of BCR/ABL in vitro and in a xenograft model of chronic myeloid leukemia
Autor(es)
Palabras clave
CRISPR/Cas9
Genome edition
BCR/ABL
Leukemia
Fecha de publicación
2017-04-08
Citación
García-Tuñón I, Hernández-Sánchez M, Ordoñez JL, Alonso-Pérez V, Álamo-Quijada M, Benito R, Guerrero C, Hernández-Rivas JM, Sánchez-Martín M. (2017). The CRISPR/Cas9 system efficiently reverts the tumorigenic ability of BCR/ABL in vitro and in a xenograft model of chronic myeloid leukemia. Oncotarget, pr 18;8(16):26027-26040. doi: 10.18632/oncotarget.15215.
Resumen
[EN]CRISPR/Cas9 technology was used to abrogate p210 oncoprotein expression in
the Boff-p210 cell line, a pro-B line derived from interlukin-3-dependent Baf/3, that
shows IL-3-independence arising from the constitutive expression of BCR-ABL p210.
Using this approach, pools of Boff-p210-edited cells and single edited cell-derived
clones were obtained and functionally studied in vitro. The loss of p210 expression
in Boff-p210 cells resulted in the loss of ability to grow in the absence of IL-3, as the
Baf/3 parental line, showing significantly increased apoptosis levels. Notably, in a
single edited cell-derived clone carrying a frame-shift mutation that prevents p210
oncoprotein expression, the effects were even more drastic, resulting in cell death.
These edited cells were injected subcutaneously in immunosuppressed mice and
tumor growth was followed for three weeks. BCR/ABL-edited cells developed smaller
tumors than those originating from unedited Boff-p210 parental cells. Interestingly,
the single edited cell-derived clone was unable to develop tumors, similar to what is
observed with the parental Baf/3 cell line.
CRISPR/Cas9 genomic editing technology allows the ablation of the BCR/
ABL fusion gene, causing an absence of oncoprotein expression, and blocking its
tumorigenic effects in vitro and in the in vivo xenograft model of CML. The future
application of this approach in in vivo models of CML will allow us to more accurately
assess the value of CRISPR/Cas9 technology as a new therapeutic tool that overcomes
resistance to the usual treatments for CML patients.
URI
ISSN
1949-2553
Collections
- GMO. Artículos [8]