Entry |
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Name |
Acute myeloid leukemia - Sus scrofa (pig)
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Description |
Acute myeloid leukemia (AML) is a disease that is characterized by uncontrolled proliferation of clonal neoplastic cells and accumulation in the bone marrow of blasts with an impaired differentiation program. AML accounts for approximately 80% of all adult leukemias and remains the most common cause of leukemia death. Two major types of genetic events have been described that are crucial for leukemic transformation. A proposed necessary first event is disordered cell growth and upregulation of cell survival genes. The most common of these activating events were observed in the RTK Flt3, in N-Ras and K-Ras, in Kit, and sporadically in other RTKs. Alterations in myeloid transcription factors governing hematopoietic differentiation provide second necessary event for leukemogenesis. Transcription factor fusion proteins such as AML-ETO, PML-RARalpha or PLZF-RARalpha block myeloid cell differentiation by repressing target genes. In other cases, the transcription factors themselves are mutated.
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Class |
Human Diseases; Cancer: specific types
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Pathway map |

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Organism |
Sus scrofa (pig) [GN: ssc]
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Gene |
100518131 | PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153] |
100621789 | PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153] |
100622559 | PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153] |
100511937 | phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649] |
100739510 | PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649] |
100623707 | PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649] |
751869 | NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580] |
100521065 | BAD; LOW QUALITY PROTEIN: bcl2-associated agonist of cell death [KO:K02158] |
100627508 | EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205] |
733648 | STAT3; signal transducer and activator of transcription 3 [KO:K04692] |
397550 | STAT5A; signal transducer and activator of transcription 5A [KO:K11223] |
397340 | STAT5B; signal transducer and activator of transcription 5B [KO:K11224] |
397208 | CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427] |
396709 | RARA; retinoic acid receptor alpha isoform X2 [KO:K08527] |
100625290 | ZBTB16; zinc finger and BTB domain-containing protein 16 [KO:K10055] |
397307 | CEBPA; CCAAT/enhancer-binding protein alpha [KO:K09055] |
100037938 | CD14; monocyte differentiation antigen CD14 precursor [KO:K04391] |
613130 | FCGR1A; high affinity immunoglobulin gamma Fc receptor I precursor [KO:K06498] |
100523899 | TCF7L1; LOW QUALITY PROTEIN: transcription factor 7-like 1 [KO:K04490] |
397297 | PPARD; peroxisome proliferator-activated receptor delta [KO:K04504] |
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Compound |
C05981 | Phosphatidylinositol-3,4,5-trisphosphate |
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Reference |
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Authors |
Steffen B, Muller-Tidow C, Schwable J, Berdel WE, Serve H. |
Title |
The molecular pathogenesis of acute myeloid leukemia. |
Journal |
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Reference |
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Authors |
Tenen DG. |
Title |
Disruption of differentiation in human cancer: AML shows the way. |
Journal |
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Reference |
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Authors |
Choudhary C, Muller-Tidow C, Berdel WE, Serve H. |
Title |
Signal transduction of oncogenic Flt3. |
Journal |
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Reference |
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Authors |
Stirewalt DL, Radich JP. |
Title |
The role of FLT3 in haematopoietic malignancies. |
Journal |
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Reference |
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Authors |
Martelli AM, Nyakern M, Tabellini G, Bortul R, Tazzari PL, Evangelisti C, Cocco L. |
Title |
Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia. |
Journal |
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Reference |
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Authors |
Lennartsson J, Jelacic T, Linnekin D, Shivakrupa R. |
Title |
Normal and oncogenic forms of the receptor tyrosine kinase kit. |
Journal |
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Reference |
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Authors |
Lorsbach RB, Downing JR. |
Title |
The role of the AML1 transcription factor in leukemogenesis. |
Journal |
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Reference |
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Authors |
Mizuki M, Schwable J, Steur C, Choudhary C, Agrawal S, Sargin B, Steffen B, Matsumura I, Kanakura Y, Bohmer FD, Muller-Tidow C, Berdel WE, Serve H. |
Title |
Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations. |
Journal |
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Reference |
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Authors |
Mueller BU, Pabst T, Fos J, Petkovic V, Fey MF, Asou N, Buergi U, Tenen DG. |
Title |
ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression. |
Journal |
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Reference |
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Authors |
Roumier C, Fenaux P, Lafage M, Imbert M, Eclache V, Preudhomme C |
Title |
New mechanisms of AML1 gene alteration in hematological malignancies. |
Journal |
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Reference |
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Authors |
Scandura JM, Boccuni P, Cammenga J, Nimer SD |
Title |
Transcription factor fusions in acute leukemia: variations on a theme. |
Journal |
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Reference |
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Authors |
Lutterbach B, Hiebert SW |
Title |
Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation. |
Journal |
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Reference |
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Authors |
Koschmieder S, Halmos B, Levantini E, Tenen DG |
Title |
Dysregulation of the C/EBPalpha differentiation pathway in human cancer. |
Journal |
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Reference |
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Authors |
Gery S, Gombart AF, Yi WS, Koeffler C, Hofmann WK, Koeffler HP |
Title |
Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia. |
Journal |
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Reference |
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Authors |
Mueller BU, Pabst T, Osato M, Asou N, Johansen LM, Minden MD, Behre G, Hiddemann W, Ito Y, Tenen DG |
Title |
Heterozygous PU.1 mutations are associated with acute myeloid leukemia. |
Journal |
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Reference |
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Authors |
Vangala RK, Heiss-Neumann MS, Rangatia JS, Singh SM, Schoch C, Tenen DG, Hiddemann W, Behre G |
Title |
The myeloid master regulator transcription factor PU.1 is inactivated by AML1-ETO in t(8;21) myeloid leukemia. |
Journal |
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Reference |
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Authors |
Muller-Tidow C, Steffen B, Cauvet T, Tickenbrock L, Ji P, Diederichs S, Sargin B, Kohler G, Stelljes M, Puccetti E, Ruthardt M, deVos S, Hiebert SW, Koeffler HP, Berdel WE, Serve H |
Title |
Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells. |
Journal |
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Reference |
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Authors |
Muller C, Yang R, Park DJ, Serve H, Berdel WE, Koeffler HP |
Title |
The aberrant fusion proteins PML-RAR alpha and PLZF-RAR alpha contribute to the overexpression of cyclin A1 in acute promyelocytic leukemia. |
Journal |
Blood 96:3894-9 (2000) |
Reference |
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Authors |
Jing Y |
Title |
The PML-RARalpha fusion protein and targeted therapy for acute promyelocytic leukemia. |
Journal |
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Reference |
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Authors |
Alcalay M, Orleth A, Sebastiani C, Meani N, Chiaradonna F, Casciari C, Sciurpi MT, Gelmetti V, Riganelli D, Minucci S, Fagioli M, Pelicci PG |
Title |
Common themes in the pathogenesis of acute myeloid leukemia. |
Journal |
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Reference |
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Authors |
Rice KL, Hormaeche I, Doulatov S, Flatow JM, Grimwade D, Mills KI, Leiva M, Ablain J, Ambardekar C, McConnell MJ, Dick JE, Licht JD |
Title |
Comprehensive genomic screens identify a role for PLZF-RARalpha as a positive regulator of cell proliferation via direct regulation of c-MYC. |
Journal |
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Reference |
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Authors |
Mikesch JH, Steffen B, Berdel WE, Serve H, Muller-Tidow C. |
Title |
The emerging role of Wnt signaling in the pathogenesis of acute myeloid leukemia. |
Journal |
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Related pathway |
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KO pathway |
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LinkDB |
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