H00003 | |
H number | H00003 |
Name | Acute myeloid leukemia |
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 DIS_PATHWAY hsa05221 Acute myeloid leukemia |
Network | nt06275 Acute myeloid leukemia nt06530(H00003) PI3K signaling |
Gene | PML-RARalpha (translocation) [HSA:5371] [KO:K10054] AML1-ETO (translocation) [HSA:861] [KO:K08367] PLZF-RARalpha (translocation) [HSA:7704] [KO:K10055] FLT3 [HSA:2322] [KO:K05092] KIT [HSA:3815] [KO:K05091] NRAS [HSA:4893] [KO:K07828] KRAS [HSA:3845] [KO:K07827] AML1 [HSA:861] [KO:K08367] CEBPA [HSA:1050] [KO:K09055] CBFB [HSA:865] [KO:K25826] CHIC2 [HSA:26511] DNMT3A [HSA:1788] [KO:K17398] ETV6 [HSA:2120] [KO:K03211] GATA2 [HSA:2624] [KO:K17894] JAK2 [HSA:3717] [KO:K04447] LPP [HSA:4026] [KO:K16676] MLLT10 [HSA:8028] [KO:K23588] NPM1 [HSA:4869] [KO:K11276] NUP214 [HSA:8021] [KO:K14317] PICALM [HSA:8301] [KO:K20044] SH3GL1 [HSA:6455] [KO:K11247] TERT [HSA:7015] [KO:K11126] |
Pathogen | - |
Env factor | - |
Carcinogen | - |
Drug | Cyclophosphamide [DR:D00287] Thioguanine [DR:D06109] Cytarabine [DR:D00168] Doxorubicin hydrochloride [DR:D01275] Daunorubicin hydrochloride [DR:D01264] Idarubicin hydrochloride [DR:D01747] Mitoxantrone hydrochloride [DR:D02166] Midostaurin [DR:D05029] (FLT3 mutation-positive) Quizartinib dihydrochloride [DR:D09956] (FLT3 internal tandem duplication) Gilteritinib fumarate [DR:D10800] (FLT3 mutation-positive) Gemtuzumab ozogamicin [DR:D03259] (CD33-positive) Glasdegib maleate [DR:D11107] Venetoclax [DR:D10679] Enasidenib mesylate [DR:D11044] (IDH2 mutation positive) Ivosidenib [DR:D11090] (susceptible IDH1 mutation) Daunorubicin and cytarabine [DR:D11390] Sargramostim [DR:D05803] Enocitabine [DR:D01633] Olutasidenib [DR:D12483] (susceptible IDH1 mutation) |
Comment | - |
Other DBs | ICD-11: 2A60 ICD-10: C92.0 MeSH: D015470 |
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JOURNAL N Engl J Med 363:2424-33 (2010) DOI:10.1056/NEJMoa1005143 PMID:25581430 (ETV6) AUTHORS Zhang MY, Churpek JE, Keel SB, Walsh T, Lee MK, Loeb KR, Gulsuner S, Pritchard CC, Sanchez-Bonilla M, Delrow JJ, Basom RS, Forouhar M, Gyurkocza B, Schwartz BS, Neistadt B, Marquez R, Mariani CJ, Coats SA, Hofmann I, Lindsley RC, Williams DA, Abkowitz JL, Horwitz MS, King MC, Godley LA, Shimamura A TITLE Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. JOURNAL Nat Genet 47:180-5 (2015) DOI:10.1038/ng.3177 PMID:21892162 (GATA2) AUTHORS Hahn CN, Chong CE, Carmichael CL, Wilkins EJ, Brautigan PJ, Li XC, Babic M, Lin M, Carmagnac A, Lee YK, Kok CH, Gagliardi L, Friend KL, Ekert PG, Butcher CM, Brown AL, Lewis ID, To LB, Timms AE, Storek J, Moore S, Altree M, Escher R, Bardy PG, Suthers GK, D'Andrea RJ, Horwitz MS, Scott HS TITLE Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. 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