Clinical course and dose response to GM-CSF of colony growth in patients with JMML withRASglycine to serine substitution. (A) Clinical course and time course study of circulating GM progenitors of cases no. 9 to 11. Mean numbers of GM colonies generated by 2 × 10⁴ PB MNCs under stimulation with or without 10 ng/mL of GM-CSF are shown. Mean numbers of GM colonies in 4 normal controls were 0 ± 0 for no factors and 0.1 ± 0.1 for GM-CSF. Dx, diagnosis; Plt-Tr, platelet transfusion. •, WBC; ■, Hb values; ▴, platelet counts. (B) Comparison of proliferative response of GM progenitors to low doses of GM-CSF among patients with JMML with NRAS or KRAS2 glycine to serine substitution, patients with JMML with the other mutations, and normal controls. Twenty thousand PB or BM MNCs were cultured in a well-containing methylcellulose culture medium supplemented with GM-CSF at concentrations of 0.01 ng/mL to 10 ng/mL. The data are expressed as a percentage of the colony growth obtained with 10 ng/mL of GM-CSF in each case. The colony growth stimulated with 0.01 ng/mL and 0.1 ng/mL of GM-CSF was significantly higher in 3 patients with Gly12Ser mutation in the RAS gene than in normal controls but comparable to the value obtained from the 3 other mutants. ∘, case no. 5; □, case no. 6; ▵, case no. 8; •, case no. 9; ■, case no. 11; ▴, The other patient with NRAS glycine to serine substitution; *, normal control 1; ◇, normal control 2; †, normal control 3.