Table S3. Potential pathogenic and therapeutic implications of the proteins significantly affected by MLN4924 treatment in
AML
Gene
Symbol/Target
Description/Pathway Somatic
Mutations*
Expression Levels*
Prognostic
Associations
Relevant
Therapeutic Agents
WSB1
Hedgehog-inducible
ubiquitin ligase
Gene fusion**
Increased
_
PF-04449913
(NCT02367456)
HMOX1
Anti-oxidant
_
Decreased in CD34+ _
cells of therapy-MDS/
AML¥
SP-2509 (LSD1
inhibitor)
Increased
GSR
GCLM
Glutathione
metabolism
GLUL
CDKN1B
ESCO2
Cell cycle regulator
SMC3 acetyl
transferase (cohesin
complex)
1/346
Increased
1/346
Increased
_
_
Small monoallelic
deletions€
1/346
Several in
_
Parthenolide,
Piperlongumine
Decreased in
complex karyotype
AML€
No correlation with
CR±
SP-2509/ panHDACIs
(panobinostat)α
Increased
_
High expression is
correlated with
increased diseasefree survival±
Cisplatin, PARP
inhibitors#
cohesins#
MRFAP1
MORF4-related gene
family
_
Increased (9/173 )
_
_
Decreased (2/173)
MORF4L2
_
Increased
MORF4L1
_
Increased (6/173)
Decreased (5/173)
NQO1
NAD(P)H
dehydrogenase
(quinone) family
_
Increased
_
NQO1 bioactivatable
drugs (β-lap or
deoxynyboquinone
[DNQ]&
MLX
Helix-loop-helix
leucine zipper
transcription factors
_
Increased
_
_
WEE1
Ser/Thr family of cell
cycle checkpoint
kinase
1/346
Increased
_
AZD1775/Vorinostat†
Cell cycle checkpoint
kinase (ATR
_
CLSPN
MK-1775 and
belinostat
(NCT02381548)
Increased
_
_
pathway)
CCPG1
Cell cycle progression _
Increased
_
_
APPBP2
Amyloid beta
precursor protein
Increased (9/173)
_
_
_
Decreased (3/173)
Increased expression
was noted also in
other members of the
amyloid family∆
SLBP
Histone RNA hairpinbinding protein
_
Increased∆∆
_
_
RRM2
Ribonucleotide
reductase generates
the
deoxyribonucleotides
required for DNA
synthesis/repair
_
Increased
_
5-Azacytidinea
(NCT0181426)
DNAJB4
DNAJ/HSP40
_
Increased
_
Nutlin-3b
NUSAP1
Nucleolar and
spindle-associated
protein 1
_
Increased
NuSAP1 Abs are
leukemia-antigens in
AML after allo-HCTc,d
_
NCF2
Neutrophil factor
associated with late
stage myeloid
differentiationf
BRD2
Bromodomain (BRD)
and extraterminal
Vitamin D3e
Increased
1/346
_
_
OTX015
(NCT01713582)
CPI-0610
(NCT02157636)
TEN-010
(NCT02308761)
BAY1238097
(NCT02369029)
BMS-986158
(NCT02419417)
ABBV-075
(NCT02391480)
(BET) proteins
CHD3
2/346
Increased
Increased in MYST3CREBBP leukemiah,I
*The information regarding the mutational status and gene expression levels were obtained from the publicly available databases:
http://cancer.sanger.ac.uk/cosmic and The Cancer Genome Atlas (TGCA) (unless reported by others).
**The Cancer Genome Atlas Research Network, NEJM 2013; 368:2059-2074
¥Liang
L, Cancer Cell 2011; 20:591-605
αFiskus
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DA, BMB Rep 2014; 47:299-310
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∆Baldus
CD, PNAS 2004; 101:3915-3920
§Haferlach
&Cao
T, Leukemia 2000; 14: 28-33
C, Haematologica 2011; 96: 829-836
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L, Leukemia 2015; 4: 807-818
∆∆Chou
ML, Physiol Genomics 2001; 5:99-111
aAimiuwu
J, Blood 2012; 119:5229-38
bHaaland
cWadia
I, Mol Cancer 2014; May 21;13:116
PP, Blood 2010;115:2077-87
dAnguille
S, Leukemia 2012; 26: 2186-2196
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E, Cell Death & Differentiation 2002; 9;85-1195
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JE, J Clin Invest 2009; 119: 1714-1726
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