Details of the Drug Combination

General Information of Drug Combination (ID: DC16NQC)

Drug Combination Name
MK-2206 Palbociclib
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs MK-2206   DMT1OZ6 Palbociclib   DMD7L94
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DIPG25
Zero Interaction Potency (ZIP) Score: 28.88
Bliss Independence Score: 29.38
Loewe Additivity Score: 10.88
LHighest Single Agent (HSA) Score: 13.76

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MK-2206
Disease Entry ICD 11 Status REF
Rectal adenocarcinoma 2B92 Phase 2 [2]
Nasopharyngeal carcinoma 2B6B Investigative [3]
MK-2206 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RAC-gamma serine/threonine-protein kinase (AKT3) TTAZ05C AKT3_HUMAN Modulator [8]
E2 ubiquitin-conjugating enzyme T (UBE2T) TT0A1R8 UBE2T_HUMAN Inhibitor [3]
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MK-2206 Interacts with 20 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Expression [9]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [7]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Increases Expression [9]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [7]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Expression [7]
Tissue factor (F3) OT3MSU3B TF_HUMAN Increases Expression [10]
Vascular endothelial growth factor receptor 1 (FLT1) OTT0OGYS VGFR1_HUMAN Decreases Expression [7]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [7]
Endothelin receptor type B (EDNRB) OTLLZV3P EDNRB_HUMAN Increases Expression [7]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Affects Response To Substance [11]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [12]
T-lymphocyte activation antigen CD80 (CD80) OTJBLUQE CD80_HUMAN Decreases Expression [7]
T-lymphocyte activation antigen CD86 (CD86) OTJCSBPC CD86_HUMAN Decreases Expression [7]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [12]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Decreases Expression [7]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Decreases Expression [13]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [12]
Interferon regulatory factor 8 (IRF8) OT8YSNI4 IRF8_HUMAN Decreases Expression [7]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [12]
Proline-rich AKT1 substrate 1 (AKT1S1) OT4JHN4Y AKTS1_HUMAN Decreases Phosphorylation [14]
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⏷ Show the Full List of 20 DOT(s)
Indication(s) of Palbociclib
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [4]
Solid tumour/cancer 2A00-2F9Z Phase 2 [5]
Schizophrenia 6A20 Terminated [6]
Palbociclib Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 4 (CDK4) TT0PG8F CDK4_HUMAN Modulator [4]
Cyclin-dependent kinase 6 (CDK6) TTO0FDJ CDK6_HUMAN Modulator [4]
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Palbociclib Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [16]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [16]
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Palbociclib Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [17]
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Palbociclib Interacts with 151 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Decreases Response To Substance [18]
CCN family member 1 (CCN1) OTKJBEMD CCN1_HUMAN Increases Expression [15]
Kinetochore protein NDC80 homolog (NDC80) OTS7D306 NDC80_HUMAN Decreases Expression [15]
Aurora kinase A (AURKA) OTMX0HYT AURKA_HUMAN Decreases Expression [15]
Monocarboxylate transporter 5 (SLC16A4) OT1YXBKC MOT5_HUMAN Increases Expression [15]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [15]
Protein Mis18-beta (OIP5) OTI5C2DE MS18B_HUMAN Decreases Expression [15]
Zinc finger protein SNAI2 (SNAI2) OT7Y8EJ2 SNAI2_HUMAN Increases Expression [15]
Protein regulator of cytokinesis 1 (PRC1) OTHD0XS0 PRC1_HUMAN Decreases Expression [15]
Mitotic checkpoint serine/threonine-protein kinase BUB1 (BUB1) OT80DZMT BUB1_HUMAN Decreases Expression [15]
Hyaluronan mediated motility receptor (HMMR) OT4M0JTZ HMMR_HUMAN Decreases Expression [15]
Cell division control protein 45 homolog (CDC45) OT6NNLOD CDC45_HUMAN Decreases Expression [15]
Geminin (GMNN) OTDYKNIY GEMI_HUMAN Decreases Expression [15]
Glutaminase kidney isoform, mitochondrial (GLS) OTGOZG2M GLSK_HUMAN Increases Expression [19]
G2/mitotic-specific cyclin-B2 (CCNB2) OTIEXTDK CCNB2_HUMAN Decreases Expression [15]
Serine protease 23 (PRSS23) OT6DQAM1 PRS23_HUMAN Increases Expression [15]
Kinesin-like protein KIF20A (KIF20A) OTXOQHE0 KI20A_HUMAN Decreases Expression [15]
Chromosome-associated kinesin KIF4A (KIF4A) OT3UWL7D KIF4A_HUMAN Decreases Expression [15]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Increases Expression [15]
Securin (PTTG1) OTIMYS4W PTTG1_HUMAN Decreases Expression [15]
G1/S-specific cyclin-E2 (CCNE2) OTBBUKQQ CCNE2_HUMAN Decreases Expression [20]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [21]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Activity [15]
Apolipoprotein E (APOE) OTFOWL2H APOE_HUMAN Increases Expression [19]
Thymidine kinase, cytosolic (TK1) OTY5JFM1 KITH_HUMAN Decreases Expression [20]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Expression [15]
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Expression [20]
SPARC (SPARC) OTPN90H0 SPRC_HUMAN Increases Expression [19]
Serine/threonine-protein kinase pim-1 (PIM1) OTWEKXTU PIM1_HUMAN Decreases Expression [21]
DNA topoisomerase 1 (TOP1) OT51O0CF TOP1_HUMAN Decreases Expression [22]
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Decreases Expression [20]
Proliferating cell nuclear antigen (PCNA) OTHZ1RIA PCNA_HUMAN Decreases Expression [15]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Affects Localization [15]
Tissue factor (F3) OT3MSU3B TF_HUMAN Increases Expression [15]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [15]
Elastin (ELN) OTFSO7PG ELN_HUMAN Increases Expression [23]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Decreases Phosphorylation [24]
Stathmin (STMN1) OTDJ4RV0 STMN1_HUMAN Decreases Expression [15]
Cadherin-2 (CDH2) OTH0Y56P CADH2_HUMAN Increases Expression [15]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [25]
Lamin-B1 (LMNB1) OT100T3P LMNB1_HUMAN Decreases Expression [15]
Ribonucleoside-diphosphate reductase large subunit (RRM1) OTXGQOR9 RIR1_HUMAN Decreases Expression [15]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [26]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Decreases Activity [27]
High mobility group protein B2 (HMGB2) OTGEGAOK HMGB2_HUMAN Decreases Expression [15]
Retinoblastoma-like protein 1 (RBL1) OTDEBFYC RBL1_HUMAN Decreases Expression [25]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Increases Expression [28]
M-phase inducer phosphatase 1 (CDC25A) OTSLKKCO MPIP1_HUMAN Decreases Expression [15]
M-phase inducer phosphatase 3 (CDC25C) OTPQI71S MPIP3_HUMAN Decreases Expression [15]
Ribonucleoside-diphosphate reductase subunit M2 (RRM2) OTOB6J6R RIR2_HUMAN Decreases Expression [15]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [29]
Dual specificity protein kinase TTK (TTK) OTBY1Z5H TTK_HUMAN Decreases Expression [15]
DNA replication licensing factor MCM7 (MCM7) OT6FXC6K MCM7_HUMAN Decreases Expression [15]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Increases Expression [15]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Expression [21]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [28]
Flap endonuclease 1 (FEN1) OT6QGG7O FEN1_HUMAN Decreases Expression [15]
Replication factor C subunit 5 (RFC5) OTAD79RT RFC5_HUMAN Decreases Expression [15]
Cyclin-F (CCNF) OTJFVU43 CCNF_HUMAN Decreases Expression [15]
Lamina-associated polypeptide 2, isoform alpha (TMPO) OTL68EL4 LAP2A_HUMAN Decreases Expression [15]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Cleavage [24]
Ran-specific GTPase-activating protein (RANBP1) OTQE226K RANG_HUMAN Decreases Expression [19]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [20]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [27]
Histone H3-like centromeric protein A (CENPA) OT0NEJ4X CENPA_HUMAN Decreases Expression [15]
Centromere protein F (CENPF) OT7AG0SW CENPF_HUMAN Decreases Expression [15]
DNA primase small subunit (PRIM1) OTWWP8Y6 PRI1_HUMAN Decreases Expression [15]
Serine/threonine-protein kinase Nek2 (NEK2) OT1H27HO NEK2_HUMAN Decreases Expression [15]
Importin subunit alpha-1 (KPNA2) OTU7FOE6 IMA1_HUMAN Decreases Expression [15]
Kinesin-like protein KIF11 (KIF11) OTHRGLCQ KIF11_HUMAN Decreases Expression [15]
Serine/threonine-protein kinase PLK1 (PLK1) OTRZX45T PLK1_HUMAN Decreases Expression [15]
DNA polymerase epsilon subunit 2 (POLE2) OTAC9V6L DPOE2_HUMAN Decreases Expression [15]
Small ribosomal subunit protein uS14 (RPS29) OTCC1872 RS29_HUMAN Increases Expression [15]
Histone H4 (H4C1) OTB71W46 H4_HUMAN Decreases Expression [15]
G-protein-signaling modulator 2 (GPSM2) OT6RPMRM GPSM2_HUMAN Decreases Expression [15]
Centromere-associated protein E (CENPE) OTQ7AP04 CENPE_HUMAN Decreases Expression [15]
Kinesin-like protein KIF23 (KIF23) OTY850JC KIF23_HUMAN Decreases Expression [15]
Forkhead box protein M1 (FOXM1) OT5887KR FOXM1_HUMAN Decreases Expression [15]
Retinoblastoma-like protein 2 (RBL2) OTBQSOE6 RBL2_HUMAN Decreases Phosphorylation [30]
Tastin (TROAP) OTC8CE0R TROAP_HUMAN Decreases Expression [15]
Cell division cycle protein 20 homolog (CDC20) OTCOEZRV CDC20_HUMAN Decreases Expression [15]
Laminin subunit beta-3 (LAMB3) OTFPU6W8 LAMB3_HUMAN Increases Expression [15]
Laminin subunit gamma-2 (LAMC2) OTJMTM72 LAMC2_HUMAN Increases Expression [15]
DNA polymerase alpha subunit B (POLA2) OTTWQ73N DPOA2_HUMAN Decreases Expression [15]
Transcription factor E2F2 (E2F2) OTO75RM7 E2F2_HUMAN Decreases Expression [15]
Max dimerization protein 4 (MXD4) OTUCXFRO MAD4_HUMAN Increases Expression [15]
Maternal embryonic leucine zipper kinase (MELK) OTEY2UQA MELK_HUMAN Decreases Expression [15]
PCNA-associated factor (PCLAF) OTMVIOUU PAF15_HUMAN Decreases Expression [15]
Condensin complex subunit 1 (NCAPD2) OT8VGE2O CND1_HUMAN Decreases Expression [15]
Kinesin-like protein KIF14 (KIF14) OTXHT4JM KIF14_HUMAN Decreases Expression [15]
Disks large-associated protein 5 (DLGAP5) OTWCN39U DLGP5_HUMAN Decreases Expression [15]
SCL-interrupting locus protein (STIL) OT9799VN STIL_HUMAN Decreases Expression [15]
Histone-lysine N-methyltransferase EZH2 (EZH2) OTIEHTKW EZH2_HUMAN Decreases Expression [15]
Cyclin-dependent kinase inhibitor 3 (CDKN3) OTBE3H07 CDKN3_HUMAN Decreases Expression [15]
Laminin subunit alpha-3 (LAMA3) OTFME7HT LAMA3_HUMAN Increases Expression [15]
Centrosomal protein of 55 kDa (CEP55) OTGSG2PA CEP55_HUMAN Decreases Expression [15]
Borealin (CDCA8) OT17D55D BOREA_HUMAN Decreases Expression [15]
PHD finger protein 19 (PHF19) OTF6RUCR PHF19_HUMAN Decreases Expression [15]
Proline/serine-rich coiled-coil protein 1 (PSRC1) OT7MDJMN PSRC1_HUMAN Decreases Expression [15]
Protein aurora borealis (BORA) OTV2ZPKP BORA_HUMAN Decreases Expression [15]
Interleukin-20 receptor subunit beta (IL20RB) OTHFXK95 I20RB_HUMAN Increases Expression [15]
Protein MCM10 homolog (MCM10) OTV0O3JN MCM10_HUMAN Decreases Expression [15]
Suppressor APC domain-containing protein 2 (SAPCD2) OTXS0EXM SAPC2_HUMAN Decreases Expression [15]
Condensin-2 complex subunit G2 (NCAPG2) OTZYENKO CNDG2_HUMAN Decreases Expression [15]
Cytoskeleton-associated protein 2-like (CKAP2L) OT4T73GG CKP2L_HUMAN Decreases Expression [15]
Kinetochore protein Spc24 (SPC24) OT1HVYV4 SPC24_HUMAN Decreases Expression [15]
Holliday junction recognition protein (HJURP) OTWMV16B HJURP_HUMAN Decreases Expression [15]
Protein DENND6B (DENND6B) OTZ006UD DEN6B_HUMAN Increases Expression [15]
DEP domain-containing protein 1B (DEPDC1B) OTMVFOT1 DEP1B_HUMAN Decreases Expression [15]
Retinol dehydrogenase 5 (RDH5) OTYBZHCC RDH5_HUMAN Increases Expression [15]
RAD51-associated protein 1 (RAD51AP1) OTXM7UTD R51A1_HUMAN Decreases Expression [15]
Sororin (CDCA5) OTZLCQ5U CDCA5_HUMAN Decreases Expression [15]
Aurora kinase B (AURKB) OTIY4VHU AURKB_HUMAN Decreases Expression [15]
Proline-rich protein 11 (PRR11) OT2JJ08Z PRR11_HUMAN Decreases Expression [15]
Lymphokine-activated killer T-cell-originated protein kinase (PBK) OT5Z27TW TOPK_HUMAN Decreases Expression [15]
Tetratricopeptide repeat protein 14 (TTC14) OTMTYOPF TTC14_HUMAN Increases Expression [15]
Serine protease FAM111A (FAM111A) OTVLARLG F111A_HUMAN Decreases Expression [15]
Cell division cycle-associated protein 3 (CDCA3) OTUI8QK3 CDCA3_HUMAN Decreases Expression [15]
Kinesin-like protein KIF2C (KIF2C) OTJ8G3NP KIF2C_HUMAN Decreases Expression [15]
BRCA1-associated RING domain protein 1 (BARD1) OTTC0Z9Y BARD1_HUMAN Decreases Expression [15]
Condensin complex subunit 3 (NCAPG) OT1AI9EO CND3_HUMAN Decreases Expression [15]
Protein PIMREG (PIMREG) OTKC8T3E PIMRE_HUMAN Decreases Expression [15]
Kinesin-like protein KIFC1 (KIFC1) OTNQDS00 KIFC1_HUMAN Decreases Expression [15]
Nucleolar and spindle-associated protein 1 (NUSAP1) OT85HIJ5 NUSAP_HUMAN Decreases Expression [15]
Rac GTPase-activating protein 1 (RACGAP1) OTQE8IEH RGAP1_HUMAN Decreases Expression [15]
DNA replication factor Cdt1 (CDT1) OTVY53VG CDT1_HUMAN Decreases Expression [15]
Protein-serine O-palmitoleoyltransferase porcupine (PORCN) OT79GAY2 PORCN_HUMAN Increases Expression [15]
Protein FAM83D (FAM83D) OTQWZ1UO FA83D_HUMAN Decreases Expression [15]
Fanconi anemia group E protein (FANCE) OTKRPBW1 FANCE_HUMAN Decreases Expression [19]
Kinetochore protein Spc25 (SPC25) OTCAS0OH SPC25_HUMAN Decreases Expression [15]
Inner centromere protein (INCENP) OT9HFRYK INCE_HUMAN Decreases Expression [15]
Anillin (ANLN) OTXJY54C ANLN_HUMAN Decreases Expression [15]
Kinesin-like protein KIF15 (KIF15) OTJRJEXL KIF15_HUMAN Decreases Expression [15]
Centromere protein M (CENPM) OTYK9KOX CENPM_HUMAN Decreases Expression [15]
Structural maintenance of chromosomes protein 4 (SMC4) OTEJE6AG SMC4_HUMAN Decreases Expression [15]
Fanconi anemia group I protein (FANCI) OTW8E3SC FANCI_HUMAN Decreases Expression [15]
Histone chaperone ASF1B (ASF1B) OTKXX12I ASF1B_HUMAN Decreases Expression [15]
Protein downstream neighbor of Son (DONSON) OTN5HE0W DONS_HUMAN Decreases Expression [15]
Carboxypeptidase A4 (CPA4) OT66MP0F CBPA4_HUMAN Increases Expression [15]
F-box only protein 5 (FBXO5) OTTR957W FBX5_HUMAN Decreases Expression [15]
Targeting protein for Xklp2 (TPX2) OTWLJYH0 TPX2_HUMAN Decreases Expression [15]
Exonuclease 1 (EXO1) OTI87RS5 EXO1_HUMAN Decreases Expression [15]
DNA replication complex GINS protein PSF2 (GINS2) OT974IYI PSF2_HUMAN Decreases Expression [15]
Small kinetochore-associated protein (KNSTRN) OTYA7UXS SKAP_HUMAN Decreases Expression [15]
Transforming acidic coiled-coil-containing protein 3 (TACC3) OTRNEZTA TACC3_HUMAN Decreases Expression [19]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Response To Substance [31]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B) OTAG24N1 CDN2B_HUMAN Decreases Response To Substance [18]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Decreases Response To Substance [31]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Decreases Response To Substance [31]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Increases Response To Substance [31]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Response To Substance [31]
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⏷ Show the Full List of 151 DOT(s)

References

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17 Progress with palbociclib in breast cancer: latest evidence and clinical considerations. Ther Adv Med Oncol. 2017 Feb;9(2):83-105.
18 p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells. Neuro Oncol. 2012 Jul;14(7):870-81. doi: 10.1093/neuonc/nos114. Epub 2012 Jun 18.
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20 Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004 Nov;3(11):1427-38.
21 Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6. Blood. 2016 Jun 9;127(23):2890-902. doi: 10.1182/blood-2015-11-683581. Epub 2016 Apr 20.
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