Table 1.

Therapeutic strategies to disrupt the BCR/ABL1 oncogene in CML by genome-editing nucleases.

Target	Cell Type	Genome Editing System	Outcomes	Reference
Fusion sequence	Boff p210 (mouse)	CRISPR/Cas9	Subcutaneous injection of edited single cell derived clones was unable to generate tumors in a CML xenograft model.	[96]
BCR exon 1	K562 (human) and patient derived CD34+ cells	ZFNs	Intravenous tail vein injection into NOD/SCID mice of the edited K562 showed a lower tumorigenic capacity in vivo. Lower proliferative capacity in vitro was observed in edited primary cells.	[95]
ABL1 exon 2	K562 (human) and patient derived CD34+ cells	CRISPR RNA-guided FokI nucleases (RFNs)	Similar results to those of their previous work. High efficiency and greater security by reducing the frequency of off-targets, compared with CRISPR/Cas9 system.	[94]
ABL1 exon 2	K562 (human) and peripheral blood mononuclear cells (PBMCs) of CML patients	CRISPR/Cas9	Virus-mediated ABL1-targeting to edit luciferase-labeled K562 into a systemic leukemia xenograft model. Bioluminescence imaging showed a significant reduction of leukemic cells in vivo.	[103]
Fusion sequence	K562 (human) and patient derived CD34+ cells	CRISPR/Cas9	Specific targeting of the BCR/ABL1 fusion sequence with a pair of guides directed towards intronic sequences of each of the genes involved in the fusion that will cause a deletion in those cells that carry the translocation.	[84]
ABL1 exon 6	Boffp210 (mouse), K562 (human), Lin- CML mouse model and patient-derived CD34+	CRISPR/Cas9	Edited HSCs from CML mouse model restored normal hematopoiesis in NOD/SCID bone marrow niche. Edited patient-derived CD34+ are capable of regenerating normal hematopoiesis in the bone marrow niche of NOD/SCID mice.	[104]