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-10 classification [BR:br08403]
 2. Neoplasms (C00-D48)
  C81-C96  Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue
   C92  Myeloid leukaemia
    H00003  Acute myeloid leukemia (AML)
Tumor markers [br08442.html]
 H00003
Cancer-accociated carbohydrates [br08441.html]
 H00003
BRITE hierarchy
Pathway
Acute myeloid leukemia
Transcriptional misregulation in cancer
Network
N00003  
Mutation-activated KIT to RAS-ERK signaling pathway
N00004  
Duplication-activated FLT3 to RAS-ERK signaling pathway
N00012  
Mutation-activated KRAS/NRAS to ERK signaling pathway
N00031  
Duplication-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-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
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
Tretinoin [DR:D00094]
Cyclophosphamide [DR:D00287]
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]
Arsenic trioxide [DR:D02106]
Sargramostim [DR:D05803]
Enocitabine [DR:D01633]
Enasidenib [DR:D10901]
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-10: 
MeSH: 
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
PMID:16236521 (gene)
  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
PMID:12194988 (gene)
  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
PMID:16757428 (gene)
  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)
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
Reference
(drug)
  Authors
Papadakis MA and McPhee SJ |(ed)
  Title
Current Medical Diagnosis & Treatment 2015, Fifty-Fourth Edition
  Journal
McGraw Hill Education
Reference
PMID:25885425 (drug)
  Authors
Coombs CC, Tavakkoli M, Tallman MS
  Title
Acute promyelocytic leukemia: where did we start, where are we now, and the future.
  Journal
Blood Cancer J 5:e304 (2015)
DOI:10.1038/bcj.2015.25

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