Table 1.

Target functions for the AML cell–specific calibrated AML model

Protein/nodeCell-specific model target function
PIM1max(3/4*FLT-ITD,TYK2,3/4*PDGFRA,FGFR1)
PIM2max(FLT-ITD,1/2*TYK2,1/2*PDGFRA)
BAD1/2*RSK+1/2*PIM1
EIF4Bmin(3,RSK+1/2*PIM1)
EIF3min(EIF4E,EIF4B)
4EBP12/3*mTORC1+1/6*EIF3+1/6*PIM2
EIF4Emax(1/2*4EBP1,S6)
S61/8*RSK+3/4*mTORC1+1/8*EIF3
BCRmax(1, 1/2*FLT-ITD)
GRB2/SOSmax(BCR,1/2*FGFR1)
RASmin(Grb2/SOS,BCR)
PI3Kmax(BCR,GRB2/SOS,1/2*PDGFRA)
RAFAVG(RAS)
MEKAVG(RAF)
ERKmax(MEK,1/2*PDGFRA)
RSKAVG(ERK)
AKTmax(PI3K,mTORC2)
mTORC2AVG(PI3K)
mTORC11/2*PRAS40+TSC2
TSC21/2*((PIM2-1)+1/2*AKT)
PRAS401/4*PIM1+5/4*AKT
CHKmax(PIM1,PIM2)
H3AVG(CHK)
cMYCmax(3/4*FGFR1,max(1,1/4*(max(PIM1,PIM2) + H3))
P27max(1,cMYC*(cMYC-2)+1/2*max(PIM1,PIM2))
Proliferation(EIF4B-2)+1/2*ERK+2/3*p27+2/3*cMYC
Apoptosis!MAX(BAD, S6, 1/2*BAD + cMyc + S6 + 2*EIF4E))
  • NOTE: Target functions are associated with the nodes and aim to capture biological relationships. MAX function corresponds to independent activation by upstream proteins, while MIN corresponds to dependent activation, such that the effect is governed by the lower expression of the two upstream proteins. “+” corresponds to an additive effect and * is used to assign magnitude of effect. Supplementary Table S1 extends this table and includes the generalized model and experimental and literature supporting evidence for each target function.