Journal: Cancers
Article Title: Ex Vivo Mitochondrial Respiration Parallels Biochemical Response to Ibrutinib in CLL Cells
doi: 10.3390/cancers13020354
Figure Lengend Snippet: Ibrutinib has similar effects on mitochondrial respiration profiles, CCL3 and 4, β-2 M, lactate dehydrogenase (LDH), Bruton tyrosine kinase (BTK) signaling and caspase-3 cleavage in chronic lymphocytic leukemia (CLL) patients independent of dose. The effect of ibrutinib treatment on basal respiration ( A ), maximal respiration ( B ), spare respiratory capacity ( C ), and respiratory control ratio ( D ) in primary CLL cells from patients pre-treatment and on ibrutinib treatment with low (blue) or standard (grey) dose. N = 14 for low dose and N = 5 for standard dose of ibrutinib. Values are mean ± S.D. **** p < 0.0001 (paired two-tailed Student’s t -test). The reduction of mitochondrial respiration parameters with low and standard dose of ibrutinib treatment is summarized for basal respiration ( E ) and maximal respiration ( F ) in freshly isolated CLL cells. N = 14 for low dose and N = 5 for standard dose of ibrutinib. Values are mean ± S.D. *** p < 0.0005, NS: non-significant (unpaired two-tailed Student’s t -test). In parallel, there is a reduction of chemokine ligands CCL3 ( G ) and CCL4 ( H ) in ibrutinib treated CLL patient plasma samples by dose. Decreased levels of β-2 M and LDH in ibrutinib treated patients compared to pre-treatment ( I , K ) and the decrease of β-2 M or LDH was similar to low or standard dose ibrutinib CLL patients ( J , L ). Demonstration of effects on pBTK, tBTK ( M ), and caspase-3 cleavage ( N ) are independent of dose. OCR: Oxygen consumption rate; resp: Respiratory; IB: Ibrutinib; TX: Treatment; Uncl. caspase-3: Uncleaved caspase-3; Cl. caspase-3: Cleaved caspase-3.
Article Snippet: Plasma CCL3 and CCL4 levels were measured pre and post treatment where matched plasma was available (Meso Scale Diagnostics, Rockville, MD [ , ].
Techniques: Control, Two Tailed Test, Isolation, Clinical Proteomics
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