Table 1 Overlap of cytokines predicted as upstream regulators (top 20 candidates; Ingenuity Pathway Analysis).

From: Stromal cells engineered to express T cell factors induce robust CLL cell proliferation in vitro and in PDX co-transplantations allowing the identification of RAF inhibitors as anti-proliferative drugs

Prediction from CXCR4/CD5 subpopulations (this study)					Predicted from this study (CXCR4/CD5 subpopulations)	Predicted from Sun et al. (lymph node vs. blood CLL cells)	Predicted from Pascutti et al. (CLL-T cell contact)
Upstream regulator	Predicted state in CXCR4^dimCD5^brigth cells	Activation z-score^a	P-value^b	Main producing cell type(s)
IL4	Activated	3.46	5.77E−29	T cells, mast cells, basophils, eosinophils	Yes	Yes	Yes
TNF	Activated	4.16	1.31E−26	Macrophages, T cells, NK cells, mast cells	Yes	Yes	Yes
IL2	Activated	3.82	2.89E−26	Activated T cells	Yes	Yes	Yes
IFNG	Activated	6.45	5.18E−25	T cells, NK cells	Yes	Yes	Yes
IL15	Activated	3.85	2.21E−20	Monocytes, macrophages, dendritic cells	Yes	Yes	Yes
CD40LG	Activated	2.81	8.34E−15	Activated T cells, dendritic cells, B cells	Yes	Yes	Yes
CSF1	Activated	4.27	1.21E−14	Monocytes, macrophages	Yes	Yes	Yes
IL33	Activated	2.80	2.03E−11	Epithelial cells, dendritic cells	Yes	Yes	Yes
IL1B	Activated	4.40	2.73E−11	Macrophages, monocytes	Yes	Yes	Yes
CSF2	Activated	4.04	2.46E−10	T cells, macrophages, endothelial cells	Yes	Yes	Yes
IL33	Activated	2.99	2.41E−07	Myeloid cells, endothelial cells	Yes	Yes	Yes
IL21	Activated	2.39	1.95E−05	Activated T cells, NK cells, dendritic cells	Yes	Yes	Yes
IL6		0.80	2.98E−06	B cells, T cells, macrophages, endothelial cells	Yes	Yes	Yes
IL5	Activated	4.16	6.58E−11	T cells, eosinophils	Yes	No	Yes
IFNA2	Activated	5.76	2.72E−10	Lymphocytes, monocytes	Yes	No	Yes
IFNL1	Activated	4.26	6.76E−05	Various cell types in response to viral infection	Yes	No	Yes
IL13	Activated	2.74	2.38E−07	T cells, macrophages, basophils	Yes	Yes	No
CSF3		0.20	2.62E−07	Epithelial cells, dendritic cells, mast cells	Yes	No	No
PRL	Activated	3.12	2.24E−06	Pituitary cells	Yes	No	No
TNFSF13B	Activated	2.00	2.31E−05	Activated T cells, B cells	Yes	No	No

Bold indicates the factors used in this study to modify HS5 cells.
Top 20 cytokines, predicted as potential upstream regulators by Ingenuity Pathway Analysis [34], causing the observed gene expression changes in CXCR4^dimCD5^bright vs. CXCR4^brightCD5^dim CLL cells.
^aZ-scores that are ≥2 correspond to predictions of highly significant activation in CXCR4^dimCD5^bright cells, while z-scores ≤ −2 correspond to highly significant inhibitions.
^bBenjamini–Hochberg corrected P-value.

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Table 1 Overlap of cytokines predicted as upstream regulators (top 20 candidates; Ingenuity Pathway Analysis).

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