Entry Name Acute myeloid leukemia - Balaenoptera acutorostrata scammoni (minke whale)
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 typesBRITE hierarchy
Pathway map Ortholog table Organism Balaenoptera acutorostrata scammoni (minke whale) [GN:
bacu ]
Gene 103008077 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
103009307 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
103007464 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
103018352 EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205 ]
102999196 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
103019365 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
102997405 signal transducer and activator of transcription 3-like [KO:K04692 ]
103008157 STAT3; signal transducer and activator of transcription 3 (acute-phase response factor) [KO:K04692 ]
103015475 signal transducer and activator of transcription 5A-like [KO:K11223 ]
103020607 signal transducer and activator of transcription 5A-like [KO:K11223 ]
103016933 MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377 ]
103018264 TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620 ]
103014919 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 KO pathway LinkDB All DBs
