KEGG   DISEASE: Acute myeloid leukemiaHelp
H00003                      Disease                                

Acute myeloid leukemia
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.
Human diseases [BR:br08402]
  Cancers of haematopoietic and lymphoid tissues
   H00003  Acute myeloid leukemia
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
Tumor markers [br08442.html]
Cancer-accociated carbohydrates [br08441.html]
BRITE hierarchy
hsa05221  Acute myeloid leukemia
hsa05202  Transcriptional misregulation in cancer
nt06275  Acute myeloid leukemia
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
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]
Benzene [CPD:C01407]
1,4-Butanediol dimethanesulfonate (Busulphan; Myleran) [CPD:C06862]
Chlorambucil [CPD:C06900]
Cyclophosphamide [CPD:C07888]
Ethylene oxide [CPD:C06548]
Melphalan [CPD:C07122]
Thiotepa [CPD:C07641]
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]
Venetoclax [DR:D10679]
Enasidenib mesylate [DR:D11044] (IDH2 mutation positive)
Daunorubicin and cytarabine [DR:D11390]
Sargramostim [DR:D05803]
Enocitabine [DR:D01633]
Gilteritinib fumarate [DR:D10800] (FLT3 mutation-positive)
Ivosidenib [DR:D11090] (susceptible IDH1 mutation)
Glasdegib maleate [DR:D11107]
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
PMID:10502596 (tumor type)
Lowenberg B, Downing JR, Burnett A.
Acute myeloid leukemia.
N Engl J Med 341:1051-62 (1999)
Steffen B, Muller-Tidow C, Schwable J, Berdel WE, Serve H.
The molecular pathogenesis of acute myeloid leukemia.
Crit Rev Oncol Hematol 56:195-221 (2005)
Kelly LM, Gilliland DG.
Genetics of myeloid leukemias.
Annu Rev Genomics Hum Genet 3:179-98 (2002)
Kiyoi H, Naoe T.
Biology, clinical relevance, and molecularly targeted therapy in acute leukemia with FLT3 mutation.
Int J Hematol 83:301-8 (2006)
PMID:6786872 (carcinogen)
Adamson RH, Seiber SM.
Chemically induced leukemia in humans.
Environ Health Perspect 39:93-103 (1981)
PMID:9055951 (carcinogen)
Savitz DA, Andrews KW.
Review of epidemiologic evidence on benzene and lymphatic and hematopoietic cancers.
PMID:3713721 (carcinogen)
Bishop JB, Wassom JS.
Toxicological review of busulfan (Myleran).
Mutat Res 168:15-45 (1986)
PMID:3865372 (carcinogen)
Cannon GW, Jackson CG, Samuelson CO Jr, Ward JR, Williams HJ, Clegg DO.
Chlorambucil therapy in rheumatoid arthritis: clinical experience in 28 patients and literature review.
Semin Arthritis Rheum 15:106-18 (1985)
PMID:15660110 (carcinogen)
Luch A.
Nature and nurture - lessons from chemical carcinogenesis.
Nat Rev Cancer 5:113-25 (2005)
PMID:12464351 (carcinogen)
Kolman A, Chovanec M, Osterman-Golkar S.
Genotoxic effects of ethylene oxide, propylene oxide and epichlorohydrin in humans: update review (1990-2001).
Mutat Res 512:173-94 (2002)

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