Table 5.

Overcoming immune evasion and targeting leukemia-promoting interactions provided by the cells of the bone marrow niche—preclinical strategies.

Leukemia-Promoting Mechanism	Treatment Strategy	Observed Effects	Models	Literature
Overexpression of adhesion molecules, Stem cell-like phenotype in IKZF1-mutated BCP-ALL	Retinoids FAK inhibitors	Abrogation of adhesion and self-renewal Increased sensitivity to dasatinib	In vitro murine and human BCP-ALL cells In vivo, murine model of Ph-positive BCP-ALL	[70]
Accumulation of leukemia-promoting myeloid cells	CSF1R blockade	Depletion of myeloid cells Increased sensitivity to nilotinib	In vivo, murine model of Ph-positive BCP-ALL	[11]
	Clodronate in liposomes	Depletion of myeloid cells Diminished leukemia burden Prolonged survival	In vivo, LN3 T-ALL transgenic murine model	[104]
Overexpression of CD47 anti-phagocytic protein by BCP- and T-ALL cells	Antibodies anti-CD47	Increased phagocytosis Inhibition of leukemia engraftment	In vitro phagocytosis assay In vivo, PDX model of BCP- and T-ALL	[105]
Insufficient T cell-dependent immune response	Monocytes engineered to express IFNα	Promotion of T cell activity Improvement of ICI and CAR T cell immunotherapy	In vivo, murine model of BCP-ALL transplanted with monocytes expressing IFNα	[106]
Leukemia-driven T cell dysfunction	T cells isolated from leukemic mice, modified with CAR	Partial leukemia eradication	In vivo, murine model of TCF3/PBX1 BCP-ALL	[159]
	T cells isolated from non-leukemic mice, modified with CAR	Complete leukemia eradication	In vivo, murine model of TCF3/PBX1 BCP-ALL	[159]

Abbreviations: BCP-ALL, B cell precursor acute lymphoblastic leukemia; CAR, chimeric antigen receptor; CSF1R, colony stimulating factor 1 receptor 1; FAK, focal adhesion kinase; IFNα, interferon α; IKZF1, IKAROS Family Zinc Finger 1; Ph-positive, Philadelphia-positive; T-ALL, T cell acute lymphoblastic leukemia; TCF3/PBX1, Transcription Factor 3/Pre-B-Cell Leukemia Homeobox 1 fusion protein.