KEGG   DISEASE: Acute myeloid leukemia (AML)Help
Entry
H00003                      Disease                                

Name
Acute myeloid leukemia (AML)
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 PML-RARalpha (in Acute promyelocytic leukemia, a subtype of AML), AML-ETO or PLZF-RARalpha block myeloid cell differentiation by repressing target genes. In other cases, the transcription factors themselves are mutated.
Category
Cancer
Brite
Human diseases [BR:br08402]
 Cancers
  Cancers of haematopoietic and lymphoid tissues
   H00003  Acute myeloid leukemia (AML)
Human diseases in ICD-11 classification [BR:br08403]
 02 Neoplasms
  Neoplasms of haematopoietic or lymphoid tissues
   Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1
    2A60  Acute myeloid leukaemias and related precursor neoplasms
     H00003  Acute myeloid leukemia (AML)
Tumor markers [br08442.html]
 H00003
Cancer-accociated carbohydrates [br08441.html]
 H00003
BRITE hierarchy
Pathway
hsa05221  Acute myeloid leukemia
hsa05202  Transcriptional misregulation in cancer
Network
N00003  Mutation-activated KIT to RAS-ERK signaling pathway
N00004  Duplication or mutation-activated FLT3 to RAS-ERK signaling pathway
N00012  Mutation-activated KRAS/NRAS to ERK signaling pathway
N00031  Duplication or mutation-activated FLT3 to RAS-PI3K signaling pathway
N00032  Mutation-activated KRAS/NRAS to PI3K signaling pathway
N00046  Mutation-activated KIT to PI3K signaling pathway
N00054  Duplication or mutation-activated FLT3 to Jak-STAT signaling pathway
N00108  AML1-ETO fusion to transcriptional activtion
N00109  PML-RARA fusion to transcriptional activtion
N00110  PLZF-RARA fusion to transcriptional activtion
N00111  AML1-ETO fusion to CEBPA-mediated transcription
N00112  AML1-ETO fusion to PU.1-mediated transcription
N00113  PML-RARA fusion to transcriptional repression
N00114  PLZF-RARA fusion to transcriptional repression
N00116  Mutation-inactivated RUNX1 to transcription
 » show all
Gene
FLT3 (mutation) [HSA:2322] [KO:K05092]
c-KIT (mutation) [HSA:3815] [KO:K05091]
N-ras (mutation) [HSA:4893] [KO:K07828]
K-ras (mutation) [HSA:3845] [KO:K07827]
PML-RARalpha (translocation) [HSA:5371] [KO:K10054]
AML1-ETO (translocation) [HSA:861] [KO:K08367]
PLZF-RARalpha (translocation) [HSA:7704] [KO:K10055]
AML1 (mutation) [HSA:861] [KO:K08367]
C/EBPalpha (mutation) [HSA:1050] [KO:K09055]
PU.1 (mutation) [HSA:6688] [KO:K09438]
Carcinogen
Benzene [CPD:C01407]
1,4-Butanediol dimethanesulfonate (Busulphan; Myleran) [DR:D00248]
Chlorambucil [DR:D00266]
Cyclophosphamide [DG:DG00675]
Ethylene oxide [CPD:C06548]
Melphalan [DG:DG00676]
Thiotepa [CPD:C07641]
Drug
Cyclophosphamide [DR:D00287]
Mechlorethamine hydrochloride [DR:D04872]
Thioguanine [DR:D06109]
Cytarabine [DR:D00168]
Doxorubicin hydrochloride [DR:D01275]
Daunorubicin hydrochloride [DR:D01264]
Idarubicin hydrochloride [DR:D01747]
Mitoxantrone hydrochloride [DR:D02166]
Gemtuzumab ozogamicin [DR:D03259]
Midostaurin [DR:D05029] (FLT3 mutation-positive)
Arsenic trioxide [DR:D02106]
Enasidenib mesylate [DR:D11044] (IDH2 mutation positive)
Sargramostim [DR:D05803]
Enocitabine [DR:D01633]
Comment
ICD-O: 9896/3, Tumor type: AML with t(8;21)(q22;q22), (AML1/ETO)
ICD-O: 9871/3, Tumor type: AML with inv(16)(p13q22) or t(16; 16)(p13, q22), (CBF-beta/MYH11)
ICD-O: 9866/3, Tumor type: Acute promyelocytic leukaemia (AML with t(15;17)(q22;q12), (PML/RAR-alpha) and variants)
ICD-O: 9897/3, Tumor type: AML with 11q23 (MLL) abnormalities
Other DBs
ICD-11: 2A60
ICD-10: C92.0
MeSH: D015470
Reference
PMID:10502596 (tumor type)
  Authors
Lowenberg B, Downing JR, Burnett A.
  Title
Acute myeloid leukemia.
  Journal
N Engl J Med 341:1051-62 (1999)
DOI:10.1056/NEJM199909303411407
Reference
  Authors
Steffen B, Muller-Tidow C, Schwable J, Berdel WE, Serve H.
  Title
The molecular pathogenesis of acute myeloid leukemia.
  Journal
Crit Rev Oncol Hematol 56:195-221 (2005)
DOI:10.1016/j.critrevonc.2004.10.012
Reference
  Authors
Kelly LM, Gilliland DG.
  Title
Genetics of myeloid leukemias.
  Journal
Annu Rev Genomics Hum Genet 3:179-98 (2002)
DOI:10.1146/annurev.genom.3.032802.115046
Reference
  Authors
Kiyoi H, Naoe T.
  Title
Biology, clinical relevance, and molecularly targeted therapy in acute leukemia with FLT3 mutation.
  Journal
Int J Hematol 83:301-8 (2006)
DOI:10.1532/IJH97.06071
Reference
PMID:6786872 (carcinogen)
  Authors
Adamson RH, Seiber SM.
  Title
Chemically induced leukemia in humans.
  Journal
Environ Health Perspect 39:93-103 (1981)
Reference
PMID:9055951 (carcinogen)
  Authors
Savitz DA, Andrews KW.
  Title
Review of epidemiologic evidence on benzene and lymphatic and hematopoietic cancers.
  Journal
Reference
PMID:3713721 (carcinogen)
  Authors
Bishop JB, Wassom JS.
  Title
Toxicological review of busulfan (Myleran).
  Journal
Mutat Res 168:15-45 (1986)
DOI:10.1016/0165-1110(86)90020-5
Reference
PMID:3865372 (carcinogen)
  Authors
Cannon GW, Jackson CG, Samuelson CO Jr, Ward JR, Williams HJ, Clegg DO.
  Title
Chlorambucil therapy in rheumatoid arthritis: clinical experience in 28 patients and literature review.
  Journal
Semin Arthritis Rheum 15:106-18 (1985)
DOI:10.1016/0049-0172(85)90028-9
Reference
PMID:15660110 (carcinogen)
  Authors
Luch A.
  Title
Nature and nurture - lessons from chemical carcinogenesis.
  Journal
Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546
Reference
PMID:12464351 (carcinogen)
  Authors
Kolman A, Chovanec M, Osterman-Golkar S.
  Title
Genotoxic effects of ethylene oxide, propylene oxide and epichlorohydrin in humans: update review (1990-2001).
  Journal
Mutat Res 512:173-94 (2002)
DOI:10.1016/S1383-5742(02)00067-4
LinkDB All DBs

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