Table 1.

Targets for eradication of LSCs in CML

Target	References	Trial	Drug(s) tested	Comments
Wnt/β-catenin MNK	Zhao et al. Cancer Cell 200772 Lim et al. PNAS 201373	+	PRI-724	Difficult target
Hedgehog	Dierks et al. Cancer Cell 200884 Zhao et al. Nature 2009	+	BMS-833923 LDE225	Failed (toxicity)
5-Lipoxygenase	Chen et al. Nat Genet 200985	+	Zileuton	Currently recruiting
BCL6	Hurtz et al. JExMed 2011	−	RI-BPI	Small molecule inhibitor in development
MYC	Reavie et al. Cancer Cell 201394 Abraham et al. Nature 201695	−	–	Difficult target
PP2A	Neviani et al. J Clin Invest 2007; 201386	−	–	Fingolimod approved for MS
PPAR-γ	Prost et al. Nature 2015125	+	Pioglitazone	Ongoing
SIRT1	Bhatia et al. Cancer Cell 2012	+	Panobinostat Vorinostat	Tested in refractory CML
Rad52	Cramer-Morales et al. Blood 201387	−	–	–
MEK	Ma et al. Sci Transl Med 201463 Packer et al. Cancer Cell 201164	+	MEK-162	Ongoing
BCL2 family	Goff et al. Cancer Stem Cell 2013	+	Obatoclax	Tested in advanced hematologic malignancies, including CML-BC
Autophagy	Bellodi et al. J Clin Invest 200990	+	Hydroxychloroquine	Ongoing (CHOICES)
PML	Ito et al. Nature 200891	+	As2O3	Ongoing
JAK2	Traer et al. Leukemia 201257 Neviani et al. J Clin Invest 201386	+	Ruxolitinib	Ongoing
ADAR1	Jiang et al. PNAS 201393	−	–	–
STAT3	Eiring et al. Leukemia 201456	−	–	Difficult target
EZH2	Xie et al.69 Scott et al.68 Cancer Discovery 2016	−	–	–
Heat shock proteins	Peng et al. Blood 200788	+	STA-9090	Ongoing
Fap1	Huang et al. Leukemia 201692	−	–	–
BCR-ABL1	Pinilla-Ibarz et al. Blood 2000115 Bocchia et al. Lancet 2005116	+	Breakpoint peptide vaccines	Suggestion of activity
PR1	Molldrem et al. Nat Med 2000117 Rezvani et al. Haematologica 2011118	+	Peptide vaccines	Negative studies
WT1	Gao et al. Blood 2000119 Dubrovsky et al. Blood 2014120	+	Peptide vaccines Peptide-specific antibody WT transduced autologous T cells	Ongoing (some)
IL1RAP	Järås M et al. PNAS 2010121	−	Antibody	–
IL3R (CD123)	Frolova et al. Br J Haematol 2014122	−	DT-conjugated antibody (SL-401; SL-501)	–