Table 4. Specificity of the... | American Society of Hematology

Table 4.

Specificity of the hypersensitivity to PEG-rHu MGDF in essential thrombocythemia: colony-forming efficiencies and sensitivities of circulating healthy and ET megakaryocytic progenitor cells to various cytokines

Titrated cytokine^4-150	Fixed cytokine^4-151	Experiment no.	Rx	Mega. colony number^‡				Conc. of cytokine at 1/2 max. colony no. (ng/mL)
				N		ET		Conc. of cytokine at 1/2 max. colony no. (ng/mL)
				min	max	min	max	N	ET	Sensitivity ratio^4-153
IL-3 alone		209	none	0	0.2	0	1.2	ND	ND	ND
		212	HU	0.2	0.6	1.4	1.6	ND	ND	ND
		255	none	0	4.0	0.6	6.4	1.7	1.8	0.9×
IL-3	MGDF	209	none	0	4.0	0.8	8.4	3.7	3.9	1.0×
		212	HU	0.2	6.0	1.6	9.0	3.1	1.7	1.8×
		255	none	0	7.8	5.2	16.4	2.9	5.2	0.6×
SCF alone		221	HU	0	5.6	2.8	10.8	ND	ND	ND
		262	none	0.4	6.8	2.4	8.4	16.0	18.0	0.9×
SCF	IL-3	257	HU	3.2	5.4	2.8	4.8	8.6	10.5	0.8×
		262	none	0.8	8.6	3.4	10.6	10.5	21.0	0.5×
SCF	MGDF	210	HU	0.4	5.4	0.4	8.8	15.0	14.0	1.1×
		221	HU	2.8	9.4	8.2	15.2	32.0	42.0	0.8×
GM-CSF alone		209	none	0	0.4	0	1.6	ND	ND	ND
		257	HU	1.8	2.8	2.0	2.8	1.9	9.8	0.2×
GM-CSF	IL-3	257	HU	3.2	5.0	2.8	3.2	13.0	5.0	2.6×
GM-CSF	MGDF	209	none	0.2	4.6	0.6	4.2	1.4	0.8	1.8×
G-CSF alone		209	none	0	0	0	0	ND	ND	ND
		227	HU	0	1.4	0	1.6	ND	ND	ND
		228	b/p	0	0.2	0.2	0.2	ND	ND	ND
G-CSF	MGDF	209	none	0	2.4	0	0.8	5.2	3.0	1.7×
		227	HU	0.4	3.0	1.0	3.0	5.5	4.2	1.3×
		228	b/p	0.6	2.4	1.0	4.8	13.0	4.3	3.0×
Epo alone		217	none	0	1.0	0	1.2	ND	ND	ND
		227	HU	0	0	0	0	ND	ND	ND
Epo	IL-3	257	HU	3.2	3.0	2.8	2.6	ND	ND
Epo	MGDF	217	none	0	1.8	0	2.2	1.15 U/mL	1.0 U/mL	1.2×
		227	HU	0.4	3.0	1.0	3.0	1.05 U/mL	1.9 U/mL	0.6×
IGF-I alone		227	HU	0	0.3	0	1.8	ND	ND	ND
		228	b/p	0	0.4	0.2	1.0	ND	ND	ND
IGF-I	MGDF	227	HU	0.4	4.2	1.0	5.0	4 × 10⁻⁹ mol/L	5 × 10⁻⁹mol/L	0.8×
		228	b/p	0.6	1.0	1.0	2.2	ND	ND	ND
IL-6 alone		210	HU	0.4	0.6	2.0	1.2	ND	ND	ND
		257	HU	1.8	2.6	2.0	2.4	< 3.0	3.0	< 1.0×
IL-6	IL-3	257	HU	3.2	4.2	2.8	4.6	4.5	8.0	0.6×
IL-6	MGDF	210	HU	0.4	3.0	0.4	4.2	6.1	5.4	1.1×
IL-11 alone		210	HU	0.4	0.4	2.0	0.4	ND	ND	ND
		257	HU	1.8	2.4	2.0	3.0	12.0	9.2	1.3×
IL-11	IL-3	257	HU	3.2	4.2	2.0	4.4	7.0	8.0	0.6×
		262	none	0.8	2.6	3.0	3.6	11.5	ND
IL-11	MGDF	210	HU	0.4	1.4	0.4	2.8	3.1	4.3	0.7×
MGDF alone		209	no	0	0.2	0	0.6	—	—	—
		210	HU	0.4	0.4	2.0	0.4	—	—	—
		217	no	0	0	0	0	—	—	—
		227	HU	0	0.4	0	1.0	—	—	—
		228	b/p	0	0.6	0.2	1.0	—	—	—
MGDF	IL-3	209	none	3.8	7.6	6.4	15.2	50	< 4	> 12.5×
		210	HU	2.0	8.8	3.2	8.8	67	0.4	181×
		217	none	1.2	5.6	2.6	8.6	115	< 0.16	718×
		227	HU	1.8	9.4	3.8	9.8	78	0.45	173×
		228	b/p	0	4.4	2.0	8.8	45	< 0.16	> 281×

Titrated cytokine^4-150	Fixed cytokine^4-151	Experiment no.	Rx	Mega. colony number^‡				Conc. of cytokine at 1/2 max. colony no. (ng/mL)
				N		ET		Conc. of cytokine at 1/2 max. colony no. (ng/mL)
				min	max	min	max	N	ET	Sensitivity ratio^4-153
IL-3 alone		209	none	0	0.2	0	1.2	ND	ND	ND
		212	HU	0.2	0.6	1.4	1.6	ND	ND	ND
		255	none	0	4.0	0.6	6.4	1.7	1.8	0.9×
IL-3	MGDF	209	none	0	4.0	0.8	8.4	3.7	3.9	1.0×
		212	HU	0.2	6.0	1.6	9.0	3.1	1.7	1.8×
		255	none	0	7.8	5.2	16.4	2.9	5.2	0.6×
SCF alone		221	HU	0	5.6	2.8	10.8	ND	ND	ND
		262	none	0.4	6.8	2.4	8.4	16.0	18.0	0.9×
SCF	IL-3	257	HU	3.2	5.4	2.8	4.8	8.6	10.5	0.8×
		262	none	0.8	8.6	3.4	10.6	10.5	21.0	0.5×
SCF	MGDF	210	HU	0.4	5.4	0.4	8.8	15.0	14.0	1.1×
		221	HU	2.8	9.4	8.2	15.2	32.0	42.0	0.8×
GM-CSF alone		209	none	0	0.4	0	1.6	ND	ND	ND
		257	HU	1.8	2.8	2.0	2.8	1.9	9.8	0.2×
GM-CSF	IL-3	257	HU	3.2	5.0	2.8	3.2	13.0	5.0	2.6×
GM-CSF	MGDF	209	none	0.2	4.6	0.6	4.2	1.4	0.8	1.8×
G-CSF alone		209	none	0	0	0	0	ND	ND	ND
		227	HU	0	1.4	0	1.6	ND	ND	ND
		228	b/p	0	0.2	0.2	0.2	ND	ND	ND
G-CSF	MGDF	209	none	0	2.4	0	0.8	5.2	3.0	1.7×
		227	HU	0.4	3.0	1.0	3.0	5.5	4.2	1.3×
		228	b/p	0.6	2.4	1.0	4.8	13.0	4.3	3.0×
Epo alone		217	none	0	1.0	0	1.2	ND	ND	ND
		227	HU	0	0	0	0	ND	ND	ND
Epo	IL-3	257	HU	3.2	3.0	2.8	2.6	ND	ND
Epo	MGDF	217	none	0	1.8	0	2.2	1.15 U/mL	1.0 U/mL	1.2×
		227	HU	0.4	3.0	1.0	3.0	1.05 U/mL	1.9 U/mL	0.6×
IGF-I alone		227	HU	0	0.3	0	1.8	ND	ND	ND
		228	b/p	0	0.4	0.2	1.0	ND	ND	ND
IGF-I	MGDF	227	HU	0.4	4.2	1.0	5.0	4 × 10⁻⁹ mol/L	5 × 10⁻⁹mol/L	0.8×
		228	b/p	0.6	1.0	1.0	2.2	ND	ND	ND
IL-6 alone		210	HU	0.4	0.6	2.0	1.2	ND	ND	ND
		257	HU	1.8	2.6	2.0	2.4	< 3.0	3.0	< 1.0×
IL-6	IL-3	257	HU	3.2	4.2	2.8	4.6	4.5	8.0	0.6×
IL-6	MGDF	210	HU	0.4	3.0	0.4	4.2	6.1	5.4	1.1×
IL-11 alone		210	HU	0.4	0.4	2.0	0.4	ND	ND	ND
		257	HU	1.8	2.4	2.0	3.0	12.0	9.2	1.3×
IL-11	IL-3	257	HU	3.2	4.2	2.0	4.4	7.0	8.0	0.6×
		262	none	0.8	2.6	3.0	3.6	11.5	ND
IL-11	MGDF	210	HU	0.4	1.4	0.4	2.8	3.1	4.3	0.7×
MGDF alone		209	no	0	0.2	0	0.6	—	—	—
		210	HU	0.4	0.4	2.0	0.4	—	—	—
		217	no	0	0	0	0	—	—	—
		227	HU	0	0.4	0	1.0	—	—	—
		228	b/p	0	0.6	0.2	1.0	—	—	—
MGDF	IL-3	209	none	3.8	7.6	6.4	15.2	50	< 4	> 12.5×
		210	HU	2.0	8.8	3.2	8.8	67	0.4	181×
		217	none	1.2	5.6	2.6	8.6	115	< 0.16	718×
		227	HU	1.8	9.4	3.8	9.8	78	0.45	173×
		228	b/p	0	4.4	2.0	8.8	45	< 0.16	> 281×

Rx = treatment with platelet lowering agent(s); b/p = busulfan in the past; HU = hydroxyurea; ND = not done.

F4-150

For titrated cytokine alone, ‘min.’ refers to no. of colonies in basal medium plus ATRA but no added cytokine; ‘max.’ refers to peak or plateau number of colonies in presence of cytokine.

F4-151

For fixed cytokine, ‘min.’ refers to no. of colonies in presence of fixed cytokine only (100 ng/mL); ‘max.’ refers to peak or plateau number of colonies in presence of both titrated and fixed cytokine. Concentration of fixed cytokine, IL-3: 10 ng/mL; MGDF: 100 ng/mL

‡

Cell number plated: 4 × 10⁴/0.1 mL culture throughout.

F4-153

Sensitivity ratio = conc. of cytokine at half max. colony no. N/ET = no. of times normal

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