Entry
Name
Acute myeloid leukemia - Sus scrofa (pig)
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.
Class
Human Diseases; Cancer: specific types
BRITE hierarchy
Pathway map
Ortholog table
Organism
Sus scrofa (pig) [GN:
ssc ]
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 ]
Compound
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Steffen B, Muller-Tidow C, Schwable J, Berdel WE, Serve H.
Title
The molecular pathogenesis of acute myeloid leukemia.
Journal
Reference
Authors
Tenen DG.
Title
Disruption of differentiation in human cancer: AML shows the way.
Journal
Reference
Authors
Choudhary C, Muller-Tidow C, Berdel WE, Serve H.
Title
Signal transduction of oncogenic Flt3.
Journal
Reference
Authors
Stirewalt DL, Radich JP.
Title
The role of FLT3 in haematopoietic malignancies.
Journal
Reference
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
Reference
Authors
Lennartsson J, Jelacic T, Linnekin D, Shivakrupa R.
Title
Normal and oncogenic forms of the receptor tyrosine kinase kit.
Journal
Reference
Authors
Lorsbach RB, Downing JR.
Title
The role of the AML1 transcription factor in leukemogenesis.
Journal
Reference
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
Reference
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
Reference
Authors
Roumier C, Fenaux P, Lafage M, Imbert M, Eclache V, Preudhomme C
Title
New mechanisms of AML1 gene alteration in hematological malignancies.
Journal
Reference
Authors
Scandura JM, Boccuni P, Cammenga J, Nimer SD
Title
Transcription factor fusions in acute leukemia: variations on a theme.
Journal
Reference
Authors
Lutterbach B, Hiebert SW
Title
Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation.
Journal
Reference
Authors
Koschmieder S, Halmos B, Levantini E, Tenen DG
Title
Dysregulation of the C/EBPalpha differentiation pathway in human cancer.
Journal
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Authors
Jing Y
Title
The PML-RARalpha fusion protein and targeted therapy for acute promyelocytic leukemia.
Journal
Reference
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
Reference
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
Reference
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
Related pathway
KO pathway
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