Table 3. In vitro studies on effects of BCR-ABL TKIs on proliferation, survival, and major functions of monocytes, macrophages, and T-lymphocytes.

Endpoints	Methods	Models	TKIs	Findings	Ref.
Monocytes/Macrophages
Proliferation/survival	Propidium iodide staining	PBMC	Imatinib	= viability	150
	Cell counting	Ovarian tumor ascites samples	Imatinib	macrophage production	96
	Cell counting	Ovarian tumor ascites samples	Dasatinib	macrophage production	96
	WST-1 assay	Human macrophages	Ponatinib	= macrophage viability	82
Monocyte differentiation	Morphology assessment	Human monocyte	Imatinib	differentiation into macrophages	95
Secretion	ELISA; qPCR	Human monocyte and macrophage; PBMC	Imatinib	TNF-α, IL-6 and IL-8 production	97 150
	ELISA	PBMC; Human monocyte and macrophage	Imatinib	= IL-10 production	150
	ELISA; Bioplex system; nitrite assay	Raw 264.7; bone-marrow derived macrophage	Dasatinib	TNF-α, IL-6, IL-12p40 and NO production	103 151
	qPCR; Bioplex system	Primary macrophage (mice)	Dasatinib	IL-10 production	103
	Bioplex system	Bone-marrow derived macrophage	Bosutinib	IL-6, IL-12p40 and TNF-α production	103
	qPCR; Bioplex system	Primary macrophage (mice)	Bosutinib	IL-10 production	103
Phagocytosis	Antigen-uptake assay	Human monocyte	Imatinib	phagocytosis	97
Cholesterol uptake	Cholesterol uptake assay	THP-1; PBMC	Imatinib	LDL uptake	100
	Cholesterol uptake assay	THP-1	Bosutinib	LDL uptake	100
MMP production/activity	Zymography	THP-1	Imatinib	MMP-2 and MMP-9 secretion and activity	100
T Lymphocytes
Proliferation/survival	3 H-TdR incorporation; CFSE staining; titrated thymidine	Naïve CD4 + T cell; Human T cell	Imatinib	T-cell proliferation	101 152 153
	Annexin V staining; Caspase assay	Human T cell	Imatinib	= T-cell apoptosis	101 152 153
	Annexin V staining	Human T cell	Imatinib	= T cell apoptosis
	CFSE dye	Human T cell	Dasatinib	T-cell proliferation	107
	Annexin V staining	PBMC; Human T cell	Dasatinib	= T cell viability	105 107
	CFSE dye	CD8 + T cell; PBMC	Nilotinib	T cell proliferation	106 154
Secretion	ELISA	Human T cell; CD8 + and CD4 + T cell	Imatinib	IFN-γ production	101 107
	ELISA; proteome profile array	Human T cell; PBMC	Dasatinib	TNF-α, IFN-γ, IL-2, IL-6, IL-17 production	105 107
	Proteome profile array	PBMC	Dasatinib	chemotactic factors secretion (SDF-1, MIP-1α, MIP-1β, MCP-1, CXCL-1)	105
	ELISPOT assay	CD8 + T cell	Nilotinib	IFN-γ production	154
Activation	Immunofluorescence	Human T cell	Imatinib	T cell activation	101
	Flow cytometry (CD25, CD69)	Human T cell	Imatinib	= T cell activation	153
	Flow cytometry (CD25, CD69)	Human T cell; PBMC	Dasatinib	T cell activation	105 107
	Flow cytometry (CD25, CD69)	Human T cell	Nilotinib	T cell activation	154

Abbreviations: CFSE, carboxyfluorescein succinimidyl ester; CXCL1, (C-X-C motif) ligand 1; ELISA, enzyme-linked immunosorbent assay; ELISPOT, enzyme-linked immunospot; IFN, interferon; IL, interleukin; MCP, monocyte chemoattractant protein-1; MIP-1, macrophage inflammatory protein 1; NO, nitric oxide; PBMC, peripheral blood mononuclear cell; qPCR, quantitative polymerase chain reaction; SDF-1, stromal cell-derived factor 1; TNF, tumor necrosis factor.