KEGG   DISEASE: 急性骨髄性白血病
エントリ  
H00003                                                             

名称    
急性骨髄性白血病
概要    
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.
カテゴリ  
がん
階層分類  
ヒト疾患 [BR:jp08402]
 がん
  造血組織およびリンパ系組織のがん
   H00003  急性骨髄性白血病
ICD-11 による疾患分類 [BR:jp08403]
 02 Neoplasms
  Neoplasms of haematopoietic or lymphoid tissues
   2A60  Acute myeloid leukaemias and related precursor neoplasms
    H00003  急性骨髄性白血病
パスウェイ 
hsa05221  急性骨髄性白血病
関連パスウェイ
hsa05200  Pathways in cancer
hsa05202  Transcriptional misregulation in cancer
ネットワーク
nt06275  Acute myeloid leukemia
  エレメント
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
病因遺伝子 
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]
発癌物質  
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]
治療薬   
ベタメタゾンリン酸エステルナトリウム [DR:D00972]
シクロホスファミド水和物 [DR:D00287]
メルカプトプリン水和物 [DR:D00161]
シタラビン [DR:D00168]
シタラビンオクホスファート水和物 [DR:D03046]
エノシタビン [DR:D01633]
フルダラビンリン酸エステル [DR:D01907]
ダウノルビシン塩酸塩 [DR:D01264]
エピルビシン塩酸塩 [DR:D02214]
アクラルビシン塩酸塩 [DR:D01911]
イダルビシン塩酸塩 [DR:D01747]
ゲムツズマブオゾガマイシン [DR:D03259] (CD33陽性)
ビンクリスチン硫酸塩 [DR:D02197]
ビンデシン硫酸塩 [DR:D01769]
トレチノイン [DR:D00094]
アザシチジン [DR:D03021]
ミトキサントロン塩酸塩 [DR:D02166]
キザルチニブ塩酸塩 [DR:D09956] (FLT3-ITD変異陽性)
ギルテリチニブフマル酸塩 [DR:D10800] (FLT3遺伝子変異陽性)
L-アスパラギナーゼ [DR:D02997]
三酸化二ヒ素 [DR:D02106]
ベネトクラクス [DR:D10679]
タミバロテン [DR:D01418]
ウベニメクス [DR:D00087]
コメント  
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
リンク   
ICD-11: 2A60
ICD-10: C92.0
MeSH: D015470
文献    
PMID:10502596 (tumor type)
  著者
Lowenberg B, Downing JR, Burnett A.
  タイトル
Acute myeloid leukemia.
  雑誌
N Engl J Med 341:1051-62 (1999)
DOI:10.1056/NEJM199909303411407
文献    
  著者
Steffen B, Muller-Tidow C, Schwable J, Berdel WE, Serve H.
  タイトル
The molecular pathogenesis of acute myeloid leukemia.
  雑誌
Crit Rev Oncol Hematol 56:195-221 (2005)
DOI:10.1016/j.critrevonc.2004.10.012
文献    
  著者
Kelly LM, Gilliland DG.
  タイトル
Genetics of myeloid leukemias.
  雑誌
Annu Rev Genomics Hum Genet 3:179-98 (2002)
DOI:10.1146/annurev.genom.3.032802.115046
文献    
  著者
Kiyoi H, Naoe T.
  タイトル
Biology, clinical relevance, and molecularly targeted therapy in acute leukemia with FLT3 mutation.
  雑誌
Int J Hematol 83:301-8 (2006)
DOI:10.1532/IJH97.06071
文献    
PMID:6786872 (carcinogen)
  著者
Adamson RH, Seiber SM.
  タイトル
Chemically induced leukemia in humans.
  雑誌
Environ Health Perspect 39:93-103 (1981)
DOI:10.1289/ehp.813993
文献    
PMID:9055951 (carcinogen)
  著者
Savitz DA, Andrews KW.
  タイトル
Review of epidemiologic evidence on benzene and lymphatic and hematopoietic cancers.
  雑誌
文献    
PMID:3713721 (carcinogen)
  著者
Bishop JB, Wassom JS.
  タイトル
Toxicological review of busulfan (Myleran).
  雑誌
Mutat Res 168:15-45 (1986)
DOI:10.1016/0165-1110(86)90020-5
文献    
PMID:3865372 (carcinogen)
  著者
Cannon GW, Jackson CG, Samuelson CO Jr, Ward JR, Williams HJ, Clegg DO.
  タイトル
Chlorambucil therapy in rheumatoid arthritis: clinical experience in 28 patients and literature review.
  雑誌
Semin Arthritis Rheum 15:106-18 (1985)
DOI:10.1016/0049-0172(85)90028-9
文献    
PMID:15660110 (carcinogen)
  著者
Luch A.
  タイトル
Nature and nurture - lessons from chemical carcinogenesis.
  雑誌
Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546
文献    
PMID:12464351 (carcinogen)
  著者
Kolman A, Chovanec M, Osterman-Golkar S.
  タイトル
Genotoxic effects of ethylene oxide, propylene oxide and epichlorohydrin in humans: update review (1990-2001).
  雑誌
Mutat Res 512:173-94 (2002)
DOI:10.1016/S1383-5742(02)00067-4

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