Page 77 - Haematologica - Vol. 105 n. 6 - June 2020

Innate drug responses in hematologic cell populations
Supplementary Figure S12). Collectively, the comparison of lineage specific drug responses between healthy indi- viduals and those derived from malignancies where the cell-of-origin is affected shows remarkable similarity.
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Figure 6. Mass cytometry (CyTOF) profiling of basal signaling patterns in nine healthy cell subsets. (A) Summary of the basal phosphorylation state of 9 signaling pro- teins associated with NF-κB, PI3K-AKT-mTOR (AKT, 4E-BP1, PLCG1 and p70-S6K), JAK-STAT (STAT1 and STAT3), MAPK (ERK and CREB) in three healthy individuals. Matched peripheral blood (PB) and bone marrow (BM) from the same healthy donors were profiled. Phosphorylation profiles for the indexed phosphoproteins were inves- tigated in corresponding cell subsets in leukemic samples: acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (B-ALL). (B) Box plot representation of population medians of p4EBP1, pPLCγ1 and pSTAT in healthy PB and BM (left) and leukemic samples (right). Center lines of boxes show medians; box limits indicate the 25th and 75th percentiles as determined by R software; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles, outliers are represented by dots; data points are plotted as open circles. *Significant difference (two-way ANOVA, Tukey’s HSD) between all corresponding populations, unless specified as not significant (ns). #Significance between AML and the corresponding healthy populations in both PB and BM. There were no significant differences between PB and BM in any population for each of the measured phosphoproteins, *P<0.05, **P<0.005, ***P<0.0005. Healthy PB and BM (n=3), AML (n=6), B-ALL (n=2). (Continued on the next page)
These results also highlight the fact that innate drug responses are often retained during cellular transforma- tion, which could guide identification of lineage specific anticancer therapies for leukemia.
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