| H00003 | |
| H番号 | 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 疾患パスウェイ hsa05221 急性骨髄性白血病 |
| ネットワーク | nt06275 Acute myeloid leukemia nt06530(H00003) PI3K signaling |
| 病因遺伝子 | 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] |
| 病原体 | - |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | ベタメタゾンリン酸エステルナトリウム [DR:D00972] トリアムシノロンアセトニド [DR:D00983] レノグラスチム [DR:D03247] 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] ベネトクラクス [DR:D10679] タミバロテン [DR:D01418] クリサンタスパーゼ [DR:D10517] ウベニメクス [DR:D00087] |
| コメント | - |
| リンク | ICD-11: 2A60 ICD-10: C92.0 MeSH: D015470 |
| 文献 | PMID:10502596 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 PMID:16236521 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 PMID:12194988 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 PMID:1652369 (PML-RARalpha translocation) 著者 de The H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A タイトル The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. 雑誌 Cell 66:675-84 (1991) DOI:10.1016/0092-8674(91)90113-D PMID:1391946 (AML1-ETO translocation) 著者 Erickson P, Gao J, Chang KS, Look T, Whisenant E, Raimondi S, Lasher R, Trujillo J, Rowley J, Drabkin H タイトル Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt. 雑誌 Blood 80:1825-31 (1992) DOI:10.1182/blood.V80.7.1825.1825 PMID:8622986 (PLZF-RARalpha translocation) 著者 Dong S, Zhu J, Reid A, Strutt P, Guidez F, Zhong HJ, Wang ZY, Licht J, Waxman S, Chomienne C, Chen Z, Zelent A, Chen SJ タイトル Amino-terminal protein-protein interaction motif (POZ-domain) is responsible for activities of the promyelocytic leukemia zinc finger-retinoic acid receptor-alpha fusion protein. 雑誌 Proc Natl Acad Sci U S A 93:3624-9 (1996) DOI:10.1073/pnas.93.8.3624 PMID:16757428 (FLT3) 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 PMID:9657776 (KIT) 著者 Beghini A, Larizza L, Cairoli R, Morra E タイトル c-kit activating mutations and mast cell proliferation in human leukemia. 雑誌 Blood 92:701-2 (1998) DOI:10.1182/blood.V92.2.701 PMID:23634996 (NRAS) 著者 Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, Robertson A, Hoadley K, Triche TJ Jr, Laird PW, Baty JD, Fulton LL, Fulton R, Heath SE, Kalicki-Veizer J, Kandoth C, Klco JM, Koboldt DC, Kanchi KL, Kulkarni S, Lamprecht TL, Larson DE, Lin L, Lu C, McLellan MD, McMichael JF, Payton J, Schmidt H, Spencer DH, Tomasson MH, Wallis JW, Wartman LD, Watson MA, Welch J, Wendl MC, Ally A, Balasundaram M, Birol I, Butterfield Y, Chiu R, Chu A, Chuah E, Chun HJ, Corbett R, Dhalla N, Guin R, He A, Hirst C, Hirst M, Holt RA, Jones S, Karsan A, Lee D, Li HI, Marra MA, Mayo M, Moore RA, Mungall K, Parker J, Pleasance E, Plettner P, Schein J, Stoll D, Swanson L, Tam A, Thiessen N, Varhol R, Wye N, Zhao Y, Gabriel S, Getz G, Sougnez C, Zou L, Leiserson MD, Vandin F, Wu HT, Applebaum F, Baylin SB, Akbani R, Broom BM, Chen K, Motter TC, Nguyen K, Weinstein JN, Zhang N, Ferguson ML, Adams C, Black A, Bowen J, Gastier-Foster J, Grossman T, Lichtenberg T, Wise L, Davidsen T, Demchok JA, Shaw KR, Sheth M, Sofia HJ, Yang L, Downing JR, Eley G タイトル Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. 雑誌 N Engl J Med 368:2059-74 (2013) DOI:10.1056/NEJMoa1301689 PMID:8955068 (KRAS) 著者 Bollag G, Adler F, elMasry N, McCabe PC, Conner E Jr, Thompson P, McCormick F, Shannon K タイトル Biochemical characterization of a novel KRAS insertion mutation from a human leukemia. 雑誌 J Biol Chem 271:32491-4 (1996) DOI:10.1074/jbc.271.51.32491 PMID:10068652 (AML1) 著者 Osato M, Asou N, Abdalla E, Hoshino K, Yamasaki H, Okubo T, Suzushima H, Takatsuki K, Kanno T, Shigesada K, Ito Y タイトル Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP2alphaB gene associated with myeloblastic leukemias. 雑誌 Blood 93:1817-24 (1999) DOI:10.1182/blood.V93.6.1817.406k36_1817_1824 PMID:15575056 (CEBPA) 著者 Smith ML, Cavenagh JD, Lister TA, Fitzgibbon J タイトル Mutation of CEBPA in familial acute myeloid leukemia. 雑誌 N Engl J Med 351:2403-7 (2004) DOI:10.1056/NEJMoa041331 PMID:25678665 (CBFB) 著者 Illendula A, Pulikkan JA, Zong H, Grembecka J, Xue L, Sen S, Zhou Y, Boulton A, Kuntimaddi A, Gao Y, Rajewski RA, Guzman ML, Castilla LH, Bushweller JH タイトル Chemical biology. A small-molecule inhibitor of the aberrant transcription factor CBFbeta-SMMHC delays leukemia in mice. 雑誌 Science 347:779-84 (2015) DOI:10.1126/science.aaa0314 PMID:10477709 (CHIC2) 著者 Cools J, Bilhou-Nabera C, Wlodarska I, Cabrol C, Talmant P, Bernard P, Hagemeijer A, Marynen P タイトル Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13). 雑誌 Blood 94:1820-4 (1999) DOI:10.1182/blood.V94.5.1820 PMID:21067377 (DNMT3A) 著者 Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T, Larson DE, Kandoth C, Payton JE, Baty J, Welch J, Harris CC, Lichti CF, Townsend RR, Fulton RS, Dooling DJ, Koboldt DC, Schmidt H, Zhang Q, Osborne JR, Lin L, O'Laughlin M, McMichael JF, Delehaunty KD, McGrath SD, Fulton LA, Magrini VJ, Vickery TL, Hundal J, Cook LL, Conyers JJ, Swift GW, Reed JP, Alldredge PA, Wylie T, Walker J, Kalicki J, Watson MA, Heath S, Shannon WD, Varghese N, Nagarajan R, Westervelt P, Tomasson MH, Link DC, Graubert TA, DiPersio JF, Mardis ER, Wilson RK タイトル DNMT3A mutations in acute myeloid leukemia. 雑誌 N Engl J Med 363:2424-33 (2010) DOI:10.1056/NEJMoa1005143 PMID:25581430 (ETV6) 著者 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 タイトル Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. 雑誌 Nat Genet 47:180-5 (2015) DOI:10.1038/ng.3177 PMID:21892162 (GATA2) 著者 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 タイトル Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. 雑誌 Nat Genet 43:1012-7 (2011) DOI:10.1038/ng.913 PMID:16247455 (JAK2) 著者 Lee JW, Kim YG, Soung YH, Han KJ, Kim SY, Rhim HS, Min WS, Nam SW, Park WS, Lee JY, Yoo NJ, Lee SH タイトル The JAK2 V617F mutation in de novo acute myelogenous leukemias. 雑誌 Oncogene 25:1434-6 (2006) DOI:10.1038/sj.onc.1209163 PMID:11433529 (LPP) 著者 Daheron L, Veinstein A, Brizard F, Drabkin H, Lacotte L, Guilhot F, Larsen CJ, Brizard A, Roche J タイトル Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23). 雑誌 Genes Chromosomes Cancer 31:382-9 (2001) DOI:10.1002/gcc.1157 PMID:8896421 (MLLT10) 著者 Tanabe S, Bohlander SK, Vignon CV, Espinosa R 3rd, Zhao N, Strissel PL, Zeleznik-Le NJ, Rowley JD タイトル AF10 is split by MLL and HEAB, a human homolog to a putative Caenorhabditis elegans ATP/GTP-binding protein in an invins(10;11)(p12;q23q12). 雑誌 Blood 88:3535-45 (1996) PMID:18308931 (NPM1) 著者 Garzon R, Garofalo M, Martelli MP, Briesewitz R, Wang L, Fernandez-Cymering C, Volinia S, Liu CG, Schnittger S, Haferlach T, Liso A, Diverio D, Mancini M, Meloni G, Foa R, Martelli MF, Mecucci C, Croce CM, Falini B タイトル Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. 雑誌 Proc Natl Acad Sci U S A 105:3945-50 (2008) DOI:10.1073/pnas.0800135105 PMID:2370860 (NUP214) 著者 von Lindern M, Poustka A, Lerach H, Grosveld G タイトル The (6;9) chromosome translocation, associated with a specific subtype of acute nonlymphocytic leukemia, leads to aberrant transcription of a target gene on 9q34. 雑誌 Mol Cell Biol 10:4016-26 (1990) DOI:10.1128/mcb.10.8.4016-4026.1990 PMID:10637483 (PICALM) 著者 Carlson KM, Vignon C, Bohlander S, Martinez-Climent JA, Le Beau MM, Rowley JD タイトル Identification and molecular characterization of CALM/AF10fusion products in T cell acute lymphoblastic leukemia and acute myeloid leukemia. 雑誌 Leukemia 14:100-4 (2000) DOI:10.1038/sj.leu.2401629 PMID:9122235 (SH3GL1) 著者 So CW, Caldas C, Liu MM, Chen SJ, Huang QH, Gu LJ, Sham MH, Wiedemann LM, Chan LC タイトル EEN encodes for a member of a new family of proteins containing an Src homology 3 domain and is the third gene located on chromosome 19p13 that fuses to MLL in human leukemia. 雑誌 Proc Natl Acad Sci U S A 94:2563-8 (1997) DOI:10.1073/pnas.94.6.2563 PMID:19147845 (TERT) 著者 Calado RT, Regal JA, Hills M, Yewdell WT, Dalmazzo LF, Zago MA, Lansdorp PM, Hogge D, Chanock SJ, Estey EH, Falcao RP, Young NS タイトル Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia. 雑誌 Proc Natl Acad Sci U S A 106:1187-92 (2009) DOI:10.1073/pnas.0807057106 |