Targeting WEE1 to enhance conventional therapies for acute lymphoblastic leukemia

Ghelli Luserna Di Rorà, Andrea; Beeharry, Neil; Imbrogno, Enrica; Ferrari, Anna; Robustelli, Valentina; Righi, Simona; Sabattini, Elena; Verga Falzacappa, Maria Vittoria; Ronchini, Chiara; Testoni, Nicoletta; Baldazzi, Carmen; Papayannidis, Cristina; Abbenante, Maria Chiara; Marconi, Giovanni; Paolini, Stefania; Parisi, Sarah; Sartor, Chiara; Fontana, Maria Chiara; De Matteis, Serena; Iacobucci, Ilaria; Pelicci, Pier Giuseppe; Cavo, Michele; Yen, Timothy J.; Martinelli, Giovanni

doi:10.1186/s13045-018-0641-1

Journal of Hematology & Oncology

Table 1 Combination index values of AZD-1775 in combination with clofarabine

From: Targeting WEE1 to enhance conventional therapies for acute lymphoblastic leukemia

			24 h			48 h			72 h
			Clofarabine (nM)			Clofarabine (nM)			Clofarabine (nM)
Cell lines			2.5	5	10	2.5	5	10	2.5	5	10
REH	AZD-1775 (nM)	6.9	0.70	0.80	0.95	0.61	0.88	0.99	0.78	1.07	1.12
		20.6	0.80	0.70	0.94	0.85	0.95	1.06	0.78	1.02	1.15
		61.7	1.32	0.70	0.91	1.61	1.38	1.05	0.90	1.10	1.09
		185.2	1.64	0.70	0.82	2.56	2.02	0.92	1.26	1.09	0.81
		555.6	0.89	0.46	0.65	1.00	0.82	0.55	0.43	0.24	0.29
		1666.7	1.10	0.43	0.76	0.33	0.34	0.34	0.62	0.64	0.68
		5000.0	2.23	1.11	0.77	1.00	0.26	1.01	1.81	1.83	1.88
NALM-6	AZD-1775 (nM)	6.9	0.24	0.45	0.55	0.60	0.46	0.75	0.73	1.06	1.15
		20.6	0.20	0.30	0.49	0.49	0.56	0.96	0.76	1.02	1.17
		61.7	0.26	0.22	0.39	0.66	0.76	0.93	0.84	1.08	1.14
		185.2	0.45	0.34	0.33	1.99	1.31	0.80	1.24	1.16	0.97
		555.6	0.63	0.39	0.27	1.38	0.93	0.66	0.85	0.66	0.57
		1666.7	0.55	0.36	0.33	9.87	0.84	1.04	0.20	0.26	0.37
		5000.0	0.84	0.64	0.71	2.05	1.98	2.19	0.49	0.55	0.66
NALM-19	AZD-1775 (nM)	6.9	0.46	0.54	0.85	0.52	0.59	0.81	1.02	1.20	1.09
		20.6	0.45	0.43	0.60	0.35	0.54	0.68	1.00	1.18	1.08
		61.7	0.56	0.39	0.62	0.38	0.41	0.43	0.91	1.01	0.92
		185.2	0.73	0.32	0.44	0.49	0.35	0.20	0.91	0.79	0.73
		555.6	0.60	0.21	0.32	0.20	0.14	0.18	0.53	0.50	0.74
		1666.7	0.68	0.27	0.41	0.21	0.15	0.27	0.69	0.75	1.10
		5000.0	1.39	0.76	0.69	0.56	0.53	0.70	1.75	1.79	2.43
RPMI-8402	AZD-1775 (nM)	6.9	0.21	0.26	0.50	0.23	0.36	1.39	8.20	1.23	1.46
		20.6	0.14	0.24	0.63	0.34	0.42	11.91	0.69	0.78	1.43
		61.7	0.22	0.21	0.62	0.77	0.53	3.17	0.55	0.83	1.26
		185.2	0.41	0.26	0.81	1.48	1.43	2.37	0.66	0.80	0.73
		555.6	0.57	0.36	0.54	0.95	0.61	0.48	0.43	0.41	0.08
		1666.7	0.60	0.38	0.32	0.55	0.33	0.21	0.28	0.10	0.12
		5000.0	0.37	0.26	0.05	0.09	0.02	0.04	0.22	0.24	0.26
Cell lines			5	10	20	5	10	20	5	10	20
CCRF-CEM	AZD-1775 (nM)	6.9	0.01	0.02	0.23	0.74	1.13	1.15	1.01	1.61	1.06
		20.6	0.01	0.01	0.08	0.92	2.29	1.30	0.43	2.41	1.02
		61.7	0.01	0.01	0.02	0.64	1.07	0.70	4.20	4.81	0.98
		185.2	0.01	0.01	0.02	1.13	0.78	0.29	0.91	0.83	0.76
		555.6	0.01	0.01	0.01	0.20	0.19	0.22	0.39	0.51	0.72
		1666.7	0.05	0.06	0.09	0.44	0.42	0.45	0.80	0.94	1.08
		5000.0	0.42	0.45	0.30	1.40	1.22	0.96	2.02	2.11	1.87
MOLT-4	AZD-1775 (nM)	6.9	0.00	0.09	0.25	1.62	8.99	8.15	1.00	1.03	1.27
		20.6	0.11	0.15	0.32	2.26	0.85	10.07	0.80	1.14	1.02
		61.7	0.32	0.24	0.40	0.69	0.75	0.55	0.95	1.19	0.62
		185.2	0.57	0.27	0.23	1.24	0.94	0.43	0.81	0.53	0.26
		555.6	0.31	0.16	0.18	0.88	0.61	0.40	0.00	0.11	0.12
		1666.7	0.40	0.28	0.30	1.31	1.42	0.42	0.31	0.31	0.32
		5000.0	1.61	1.76	1.66	6.06	5.49	5.24	0.92	2.04	0.93

The table reports the Combination Index (CI) value for each combination of drugs. CI < 1 indicates synergism, CI = 1 indicates additivity and CI > 1 indicates antagonism

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