MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v04/MSV000089035/primaryOK2000000Timothy J. Leyhttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=ba5c6b8ada4347c98576ce1432116bfctimley@wustl.eduMassIVE79UNIMOD:21 - "Phosphorylation."UNIMOD:4 - "Iodoacetamide derivative."UNIMOD:27 - "Pyro-glu from E."UNIMOD:1 - "Acetylation."UNIMOD:26 - "S-carbamoylmethylcysteine cyclization (N-terminus)."UNIMOD:35 - "Oxidation or Hydroxylation."ProteomicsQ Exactive PlusHomo Sapiens (ncbitaxon:9606)Washington University in St. LouisWe have developed a deep-scale proteome and phosphoproteome database from 44 representative acute myeloid leukemia (AML) patients from the LAML TCGA dataset and 6 healthy bone marrow-derived controls. After confirming data quality, we orthogonally validated several previously undescribed features of AML revealed by the proteomic data. We identified examples of posttranscriptionally regulated proteins both globally (ie, in all AML samples) and also in patients with recurrent AML driver mutations. For example, samples with IDH1/2 mutations displayed elevated levels of the 2-oxoglutarate-dependent histone demethylases KDM4A/B/C, despite no changes in messenger RNA levels for these genes; we confirmed this finding in vitro. In samples with NPMc mutations, we identified several nuclear importins with posttranscriptionally increased protein abundance and showed that they interact with NPMc but not wild-type NPM1. We identified 2 cell surface proteins (CD180 and MRC1/CD206) expressed on AML blasts of many patients (but not healthy CD34+ stem/progenitor cells) that could represent novel targets for immunologic therapies and confirmed these targets via flow cytometry. Finally, we detected nearly 30 000 phosphosites in these samples; globally, AML samples were associated with the abnormal phosphorylation of specific residues in PTPN11, STAT3, AKT1, and PRKCD. FLT3-TKD samples were associated with increased phosphorylation of activating tyrosines on the cytoplasmic Src-family tyrosine kinases FGR and HCK and related signaling proteins. PML-RARA-initiated AML samples displayed a unique phosphorylation signature, and TP53-mutant samples showed abundant phosphorylation of serine-183 on TP53 itself. This publicly available database will serve as a foundation for further investigations of protein dysregulation in AML pathogenesis.Proteomic and phosphoproteomic landscapes of acute myeloid leukemia.Kramer Michael H MH, Zhang Qiang Q, Sprung Robert R, Day Ryan B RB, Erdmann-Gilmore Petra P, Li Yang Y, Xu Ziheng Z, Helton Nichole M NM, George Daniel R DR, Mi Yiling Y, Westervelt Peter P, Payton Jacqueline E JE, Ramakrishnan Sai M SM, Miller Christopher A CA, Link Daniel C DC, DiPersio John F JF, Walter Matthew J MJ, Townsend R Reid RR, Ley Timothy J TJnPKC-delta, src Protein-Tyrosine, RAR, PRKBA, Akt/PKB, alpha-Ketoglutarate, Materials, acute non lymphoblastic leukemia, Myeloid, DAKT1/PKB, tyrosine-protein kinase receptor FLT3, A4, cd206, Integral, AKT1, phosphorylation, 2 Ketoglutaric Acid, 2-Amino-3-hydroxypropionic acid, Mutations, MYL, protein polypeptide chains, Trim19, unspecified, FET GROWTH RETARD WTNOS, bbl, FET GRWTH RET 1250-1499G, 1, Scanning Transmission Electron Microscopy, 2, Kinase, fetal SGA, primary stem, Cell Sortings, JTK9, Non Polyadenylated, Id-1, PICD, Disodium Salt, CFC, gamma sarcoglycan, PKC-delta, alpha-ketoglutarate, stimulation by symbiont of host programmed cell death, BCC7, Idpc, plant peltate hair, Surface, 1200009E24Rik, src Tyrosine Kinases, alpha-Oxoglutarate, proteins, SAP-2, amlcr1, fetal growth retardation, Fetal growth retardation NOS, Poor fetal growth, RacPK, FGR - Fetal growth retardation, Transportins, 2-Ketoglutaric Acid, Calcium Ketoglutarate, 500-749 grams, IDPC, Red, p55c-fgr, Surface Protein, FET GRWTH RET 1750-1999G, src-Family Kinase, single organism signaling, acute myelogenous, Diagnostic Findings, Cell Sorting, ADMIO, foetal Growth retardation, Data Set, Polyadenylated, src Protein-Tyrosine Kinases, Dipotassium Salt, 2-oxopentanedioic acid, tklal-a, hematopoietic cell kinase, AKT/PKB, Transportin, Lysine Demethylase, Flk-2, Fetal Growth Retardation, Histone Arginine, JHDM3A, Qualities, Flk2, FLK2, src-Family Tyrosine, p-Akt, sarcoglycan, bfy, macrophage mannose receptor 1-like protein 1, evi-1, B23NP, CLEC13DL, Polyadenylated Messenger RNA, Idh-1, Cell Membrane Protein, src Tyrosine, Non Polyadenylated mRNA, protein_coding_transcript, FET GROWTH RET 500-749G, Myeloblastic, xAct, Membrane-Associated, progressive multifocal, alpha Oxoglutarate, Acute Myeloid Leukemia, Cell Membrane Proteins, Fluorescence-Activated Cell, dAKT/dPKB, PKB/dAKT, Non-Polyadenylated mRNA, AW109958, src Tyrosine Kinase, Sodium Salt, primary axis, Material, 35kD dystrophin-associated glycoprotein, activation by symbiont of host programmed cell death, Cells, Hctk, bhy, Foetal growth retardation, Oxogluric Acid, Diammonium Salt, 749 grams, Clinical Finding, Poly(A) RNA, RAC-ALPHA, atypia, DmelCG4006, Importin, multinuclear leukocyte, hemopoietic cell kinase, Importins, regulation by symbiont of host system process, peltate hair, Accuracies, ATAKT1, stalk, protein-containing complex, LFS1, Fluorescence-Activated, connexin43, Fluorescence-Activated Cell Sortings, Microfluorometry, Src Family Tyrosine Kinase, v-akt, akt-1, src Family Kinase, LY64, 750-1, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, Membrane-Associated Protein, Gene Products, ALPS3, causality., Yellow, atypical, src Kinase, MAM, gamma-SG, p59Hck, Cytofluorometry, acute myeloid leukaemia (AML), Cell Membrane, Intrauterine growth retardation, Leukemia, dkdm4a, clec13d, Fetal growth retardation NOS (disorder), Flow Cytofluorometries, RNF71, HIES, Monosodium Salt, messenger RNA, tklal, PP8675, pebp2ab, culm, Calcium alpha-Ketoglutarate, MRC1L1, hies, p55-Fgr, BMK, Bmk, Arginine Demethylases, template RNA, intrauterine Growth retardation, Histone Lysine Demethylase, Ly78, AKT, Akt, Ly72, 000-1, Flow, 000-2, Flow Microfluorometries, Cytometry, PTP1D, Jmjd2a, Fetal growth retardation, B-cell/myeloid kinase, Sortings, leukemia, Data Accuracies, 2-Oxoglutarate, 2-ketoglutarate, RNA, FLT3, mKIAA0677, AW536184, D4Ertd222e, 35 kDa dystrophin-associated glycoprotein, FLT-3, p61Hck, hemolysin activity, akt, Histone Lysine, Progenitor Cells, Proteins, Phosphorylations, Messenger RNA, Cell Surface, Cell Surface Protein, AW259686, DAkt1, STK-1, Flow Cytometries, defective, DAKT1, Histone, PTP-1D, Cell, CD135, SGCG, AML, Serin, MR, PKB, native protein, CWS6, medulla ossium, Poly(A)+ mRNA, PKB-ALPHA, Jmjd2, INSDC_feature:mRNA, Data Quality, F18A8_2, foetal small for gestational Age, CG4006, scales, aml1-evi-1, Flow Microfluorometry, Demethylases, Cell Surface Proteins, Membrane Associated Protein, stem cell tyrosine kinase 1, Dakt1, aml, Yellow Marrow, Calcium, 2-Ketoglutarate, pkb, DMDA1, mRNA, tyrosine-protein kinase receptor flk-2, medullary bone, 2700084A17Rik, Microsomic baby, src Family Tyrosine Kinases, Accuracy, Monopotassium Salt, ion(2-), 2 Oxoglutaric Acid, Gene Proteins, dAkt/PKB, src, Acute, 1110034C02Rik, signalling process, 750-999 grams, BPTP3, PML, fetal liver kinase 2, polymorphonuclear leucocyte, Cx43, Gja-1, Polyadenylated mRNA, nr1b1, Integral Membrane Proteins, MGC130048, B23, scale tissue, alpha Ketoglutaric Acid, FET GROWTH RET 750-999G, Feature, Surface Proteins, positive regulation by symbiont of host non-apoptotic programmed cell death, protein, Membrane-Associated Proteins, Foundation, Poor fetal growth state, BLAST, Tp53, Histone Arginine Demethylases, p59-HCK/p60-HCK, JMJD2, CG15835, Calcium Salt (2:1), wmfl, medulla ossea, AI314845, Mother Cells, pathogenesis, intrauterine Growth restriction, Flow Microfluorimetry, TRIM19, protein aggregate, FL cytokine receptor, Protein-Tyrosine Kinases, src Kinases, FET GRWTH RET 1000-1249G, p56-HCK/p59-HCK, AI385711, FET GRWTH RET 1500-1749G, Fluorescence Activated Cell Sorting, Fetal growth retardation (disorder), Acute Myeloblastic Leukemia, Polyadenylated Messenger, RP105, fetal growth restriction, 500-1, leukoencephalopathy, Histone Lysine Demethylases, aml1, PKB|Akt, Red Marrow, XAML, c-src2, fetus small for gestational Age, Ketoglutaric Acid, 250-1, 2-amino-3-hydroxypropanoic acid, JMJD2A, Therapies, gamma-sarcoglycan, Membrane Associated Proteins, ANLL, CD206, Flt-3, Membrane Protein, Flow Cytofluorometry, less than 500 grams, Therapy, SIGNS SYMPTOMS, AW546267, Fluorescence-Activated Cell Sorting, dakt, aberrant, IDH, src-Family, DESC, aprf, foetal SGA, SG-gamma, PTP2C, IDP, prkcd, l(3)89Bq, Oxoglutarates, CD34, IDCD, src-Family Tyrosine Kinase, Microfluorimetry, Electron Microscopy, unspecified [weight], TDRD14A, PKB/Akt, PKB/AKT, Lysine Demethylases, Colony-Forming Unit, dAkt, dAKT, Stem Cell, 3-Hydroxyalanine, 2 Oxoglutarate, Syp, pkc-delta2, modulation by symbiont of host system process, HCK, Genetic Materials, MMR, NOS, DAkt, Genetic Material, APRF, YCL060C, l(3)04226, Mother Cell, AU040960, Acute myelogenous leukemia, DPKB, Cytofluorometries, PKCdelta, SRC2, fetal small for gestational Age, pAkt, NPM, Npm, medulla of bone, Stem, FET GROWTH RET 2500+G, susceptibility to, 2-Oxoglutaric Acid, Shp2, SHP2, mmr, Colony Forming Units, stat3, Quality, IUGR - Intrauterine growth retardation, foetal growth retardation, Features, gamma (35kDa dystrophin-associated glycoprotein), Treatments, Aprf, v-akt1, Tyrosine Kinase, Npm1, npkc-delta, DMDA, Dakt, acute myeloid leukemia (AML), Patient, dPKB, aml-1, c-fgr, Histone Demethylase, STEM, P53, Microsomia, p44, Cistron, CVID9, L Serine, Exportin, FET GRWTH RET 2000-2499G, 499 grams, L-Serine, Proteomes, Bone, Integral Membrane, AU042049, DRAC-PK85, Exportins, SHPTP2, SGCG_HUMAN, 249 grams, NS1, Colony-Forming Units, AI849071, p53, Progenitor Cell, src-Family Tyrosine Kinases, Gene, hematopoietic progenitor cell antigen CD34, C-type lectin domain family 13 member D-like, Data Qualities, TYPE, Symptoms and Signs, FET GROWTH RETARD <500G, Potassium Salt, DAGA4, Dpkb, Blasts, src Family Kinases, acute non lymphoblastic leukaemia, polypeptide chain, Demethylase, Messenger, 999 grams, AI661194, Marrow, 35DAG, SHP-2, acute myeloid, IUGR, Finding, HEL-216, AI788952, DmelCG15835, SCG3, Progenitor, Runx-1, dJMJD2(1), STK1, B230315G04, Genetic, Karyopherin, F18A8.2, Microfluorometries, Tyrosine Kinases, Mother, FLK-2, tyrosine-protein kinase FLT3, causes, dKDM4A, E030024J03Rik, 500+ grams, alpha Ketoglutarate, may1, D14Ertd420e, Trp53, Clients, Cnx43, DRAC-PK, p58c-fgr, Characteristics, TRP53, K+ transporter 1, 2-oxoglutarate, Cytometries, SH-PTP3, 2 Ketoglutarate, SH-PTP2, fetal Growth retardation, Colony Forming Unit, activation by organism of non-apoptotic programmed cell death in other organism, protein complex, axis, total expressed protein, Scanning Transmission, Pkcd, rara2a, Cistrons, Client, LGMD2C, Xp53, p58-Fgr, Signs and Symptoms, Characteristic, PKC[d], pkcd, laloo, natural protein, NR1B1, Protein, HEL-S-26, MAY1, Membrane Proteins, FGR, Xstat3, D-Akt, Polyadenylated RNA, cbfa2, PKCD, Data Base, NO38, Poly(A)+ RNA, scale, jtk9, Poly(A) Tail, akt1, dAkt1, Xaml1, Kinases, DRAC-PK66, Non-Polyadenylated, RARalpha1, Membrane, Fms-like tyrosine kinase 3, F630107B15, p56Hck, Protein Gene Products, Nr1b1, Calcium alpha Ketoglutarate, dakt1, Integral Membrane Protein, CLEC13D, Therapeutic, Data, foetus small for gestational Age, PKBalpha, SCARMD2, alpha-Ketoglutaric Acid, Sorting, ptp-2, Cx43alpha1, Treatment, dAKT1, RAC, Rac, POTASSIUM TRANSPORTERMyelogenous Leukemias, Myelocytic, leukemia, Myelogenous, Acute Myeloblastic, acute myeloblastic leukemia, M1, M2, acute myelogenous leukemia, Nonlymphocytic Leukemia, acute non lymphoblastic leukemia, Myeloid, acute myeloblastic leukaemia, acute myelogenous leukaemia, Myelocytic Leukemia, Leukemias, Acute Myeloid, Acute Myelocytic Leukemias, AML, Acute Myelocytic Leukemia, Nonlymphoblastic Leukemia, Nonlymphocytic Leukemias, Nonlymphoblastic, acute non lymphoblastic leukaemia, Acute Myeloid Leukemias, M1., Myeloid Leukemias, Acute Myelocytic, Acute Nonlymphoblastic, acute myeloid, Acute Nonlymphocytic, Myeloblastic Leukemia, Acute Myelogenous Leukemia, acute, Acute myelogenous leukemia, Leukemia, Myeloblastic, Acute Myelogenous, Acute Myeloblastic Leukemia, susceptibility to, Myeloblastic Leukemias, Acute Myeloid Leukemia, acute myeloid leukemia, acute myeloid leukaemia, Myelogenous Leukemia, Acute Nonlymphocytic Leukemias, Nonlymphocytic, Acute Myeloid Leukemia without Maturation, Acute Myeloid Leukemia with Maturation, Acute, Acute Nonlymphoblastic Leukemia, Acute Nonlymphocytic Leukemia, Acute Nonlymphoblastic Leukemias, Acute Myeloblastic Leukemias, Myeloid Leukemia, Acute Myelogenous Leukemias, Myelocytic Leukemias, ANLL, Nonlymphoblastic Leukemias, AML - acute Myeloid Leukemia, acute myelogenousMyelogenous Leukemias, Myelocytic, leukemia, Myelogenous, Acute Myeloblastic, acute myeloblastic leukemia, M1, M2, acute myelogenous leukemia, Nonlymphocytic Leukemia, acute non lymphoblastic leukemia, Myeloid, acute myeloblastic leukaemia, acute myelogenous leukaemia, Myelocytic Leukemia, Leukemias, Acute Myeloid, Acute Myelocytic Leukemias, AML, Acute Myelocytic Leukemia, Nonlymphoblastic Leukemia, Nonlymphocytic Leukemias, Nonlymphoblastic, acute non lymphoblastic leukaemia, Acute Myeloid Leukemias, M1., Myeloid Leukemias, Acute Myelocytic, Acute Nonlymphoblastic, acute myeloid, Acute Nonlymphocytic, Myeloblastic Leukemia, Acute Myelogenous Leukemia, acute, Acute myelogenous leukemia, Leukemia, Myeloblastic, Acute Myelogenous, Acute Myeloblastic Leukemia, susceptibility to, Myeloblastic Leukemias, Acute Myeloid Leukemia, acute myeloid leukemia, acute myeloid leukaemia, Myelogenous Leukemia, Acute Nonlymphocytic Leukemias, Nonlymphocytic, Acute Myeloid Leukemia without Maturation, Acute Myeloid Leukemia with Maturation, Acute, Acute Nonlymphoblastic Leukemia, Acute Nonlymphocytic Leukemia, Acute Nonlymphoblastic Leukemias, Acute Myeloblastic Leukemias, Myeloid Leukemia, Acute Myelogenous Leukemias, Myelocytic Leukemias, ANLL, Nonlymphoblastic Leukemias, AML - acute Myeloid Leukemia, acute myelogenousplan specification, total expressed protein, scale tissue, method, scales, method used in an experiment., scale, study protocol, Proteomes, plant peltate hair, peltate hair0PXD032183falseProteomic and Phosphoproteomic Landscapes of Acute Myeloid LeukemiaDeep-scale proteome and phosphoproteome protocol benchmark.Thu Mar 10 10:01:00 GMT 2022MSV00008903535895896