Acute myeloid leukemia (Homo sapiens)

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AKT3PAKT2P3-5, 7, 11...1162328172415626NucleusERM6: ErythroleukemiaM7: Acute megakaryotic leukemiaProliferative genesM0M4: Acute myelomonocytic leukemiaLegendM0: Acute myeloblastic leukemia with minimal differentiationM2: Acute myeloblastic leukemia with maturationM3: Acute promyelocytic leukemiaActivating mutationAML-ETOProliferationM1: Acute myeloblastic leukemia without maturationM5: Acute monocytic leukemiaDasatinibKIT19MidostaurinFLT3-ITD10, 14, 27Retinoic acidGRB2SOS1RUNX118, 25Arsenic trioxideSOS2GLI1PIM1HRASKRASNRASARAFRAF1PPBRAFPSTAT3STAT5ASTAT5BPIK3CAPIK3CBPIK3CDPIK3R1PIK3R2PIK3R3PIP3AKT1PPPCHUKPIKBKBPPIKBKGBADPPMTORPPNFKB1RELAPMAP2K1PPPMAPK1PPMAPK3PPMAP2K2PPEIF4EBP1PPPRPS6KB2RPS6KB1PPPPIM2BCL2A1CEBPESPI1RUNX1T1RUNX1PMLRARARARAZBTB16Anti-apoptotic genesProtein synthesisCell survivalAnti-apoptosisCEBPACEBPA20JUP1717CCND1MYCPPARDDUSP6MYCCCNA2CCNA1PML-RARalphaPLZF-RARalphaLEF1TCF7TCF7L2TCF7L1CD14FCGR1AITGAMSPI19CSF1RPER27CEBPA targetgenesCSF1RCSF2MPOIL3ProliferationBlock of differentiationBlock of differentiationProliferation6Retinoic acidM2M4M1, M2, M4M0, M4, M5, M6M3Inactivating mutationRadotinibGilteritinibSunitinibLestaurtinibCrenolanibSorafenibPonatinibQuizartinibIbrutinibFostamatinibEntospletinibFLT3-ITD immature form


Description

Acute Myeloid Leukemia is a cancer of the myeloid cell line of blood cells of the bone marrow. Rapid growth of cancer cells leads to the accumulation of neoplastic blasts in the node marrow, and interferes with the production of normal blood cells.

AML develops as the consequence of a series of genetic changes. Two major types of changes have been described as crucial for leukemic transformation: 1. Disordered cell growth and up-regulation of cell survival genes. The most common of these activating events are in the RTK Flt3, in N-Ras and K-Ras, in Kit, and sometimes in other RTKs. 2. Alterations in transcription factors regulating hematopoietic differentiation. Transcription factor fusion proteins such as AML-ETO, PML-RARalpha or PLZF-RARalpha block myeloid cell differentiation by repressing target genes. Sometimes the transcription factors themselves are mutated.

This description was adapted from KEGG (https://www.kegg.jp/pathway/map=map05221), Wikipedia (https://en.wikipedia.org/wiki/Acute_myeloid_leukemia) and Wolters Kluwer Up to Date (https://www.uptodate.com/contents/molecular-genetics-of-acute-myeloid-leukemia#:~:text=Acute%20myeloid%20leukemia%20(AML)%20develops,bone%20marrow%20and%20peripheral%20blood.).

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Bibliography

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  1. Choudhary C, Olsen JV, Brandts C, Cox J, Reddy PN, Böhmer FD, Gerke V, Schmidt-Arras DE, Berdel WE, Müller-Tidow C, Mann M, Serve H; ''Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes.''; Mol Cell, 2009 PubMed Europe PMC Scholia
  2. Zhou C, Du J, Zhao L, Liu W, Zhao T, Liang H, Fang P, Zhang K, Zeng H; ''GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia.''; Cell Death Dis, 2021 PubMed Europe PMC Scholia
  3. Roumier C, Fenaux P, Lafage M, Imbert M, Eclache V, Preudhomme C; ''New mechanisms of AML1 gene alteration in hematological malignancies.''; Leukemia, 2003 PubMed Europe PMC Scholia
  4. Tenen DG; ''Disruption of differentiation in human cancer: AML shows the way.''; Nat Rev Cancer, 2003 PubMed Europe PMC Scholia
  5. Gómez AM, Schwaller B, Porzig H, Vassort G, Niggli E, Egger M; ''Increased exchange current but normal Ca2+ transport via Na+-Ca2+ exchange during cardiac hypertrophy after myocardial infarction.''; Circ Res, 2002 PubMed Europe PMC Scholia
  6. Choudhary C, Müller-Tidow C, Berdel WE, Serve H; ''Signal transduction of oncogenic Flt3.''; Int J Hematol, 2005 PubMed Europe PMC Scholia
  7. Steffen B, Müller-Tidow C, Schwäble J, Berdel WE, Serve H; ''The molecular pathogenesis of acute myeloid leukemia.''; Crit Rev Oncol Hematol, 2005 PubMed Europe PMC Scholia
  8. Alcalay M, Orleth A, Sebastiani C, Meani N, Chiaradonna F, Casciari C, Sciurpi MT, Gelmetti V, Riganelli D, Minucci S, Fagioli M, Pelicci PG; ''Common themes in the pathogenesis of acute myeloid leukemia.''; Oncogene, 2001 PubMed Europe PMC Scholia
  9. Lorsbach RB, Downing JR; ''The role of the AML1 transcription factor in leukemogenesis.''; Int J Hematol, 2001 PubMed Europe PMC Scholia
  10. Stirewalt DL, Radich JP; ''The role of FLT3 in haematopoietic malignancies.''; Nat Rev Cancer, 2003 PubMed Europe PMC Scholia
  11. Fernandez S, Desplat V, Villacreces A, Guitart AV, Milpied N, Pigneux A, Vigon I, Pasquet JM, Dumas PY; ''Targeting Tyrosine Kinases in Acute Myeloid Leukemia: Why,Who and How?''; Int J Mol Sci, 2019 PubMed Europe PMC Scholia
  12. ''''; , PubMed Europe PMC Scholia
  13. Müller C, Yang R, Park DJ, Serve H, Berdel WE, Koeffler HP; ''The aberrant fusion proteins PML-RAR alpha and PLZF-RAR alpha contribute to the overexpression of cyclin A1 in acute promyelocytic leukemia.''; Blood, 2000 PubMed Europe PMC Scholia
  14. Müller-Tidow C, Steffen B, Cauvet T, Tickenbrock L, Ji P, Diederichs S, Sargin B, Köhler G, Stelljes M, Puccetti E, Ruthardt M, deVos S, Hiebert SW, Koeffler HP, Berdel WE, Serve H; ''Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells.''; Mol Cell Biol, 2004 PubMed Europe PMC Scholia
  15. Rice KL, Hormaeche I, Doulatov S, Flatow JM, Grimwade D, Mills KI, Leiva M, Ablain J, Ambardekar C, McConnell MJ, Dick JE, Licht JD; ''Comprehensive genomic screens identify a role for PLZF-RARalpha as a positive regulator of cell proliferation via direct regulation of c-MYC.''; Blood, 2009 PubMed Europe PMC Scholia
  16. Koschmieder S, Halmos B, Levantini E, Tenen DG; ''Dysregulation of the C/EBPalpha differentiation pathway in human cancer.''; J Clin Oncol, 2009 PubMed Europe PMC Scholia
  17. ''KEGG Acute myeloid leukemia pathway''; https://www.genome.jp/pathway/hsa05221,
  18. Lutterbach B, Hiebert SW; ''Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation.''; Gene, 2000 PubMed Europe PMC Scholia
  19. Jing Y; ''The PML-RARalpha fusion protein and targeted therapy for acute promyelocytic leukemia.''; Leuk Lymphoma, 2004 PubMed Europe PMC Scholia
  20. Mueller BU, Pabst T, Fos J, Petkovic V, Fey MF, Asou N, Buergi U, Tenen DG; ''ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression.''; Blood, 2006 PubMed Europe PMC Scholia
  21. Lennartsson J, Jelacic T, Linnekin D, Shivakrupa R; ''Normal and oncogenic forms of the receptor tyrosine kinase kit.''; Stem Cells, 2005 PubMed Europe PMC Scholia
  22. Vangala RK, Heiss-Neumann MS, Rangatia JS, Singh SM, Schoch C, Tenen DG, Hiddemann W, Behre G; ''The myeloid master regulator transcription factor PU.1 is inactivated by AML1-ETO in t(8;21) myeloid leukemia.''; Blood, 2003 PubMed Europe PMC Scholia
  23. Mikesch JH, Steffen B, Berdel WE, Serve H, Müller-Tidow C; ''The emerging role of Wnt signaling in the pathogenesis of acute myeloid leukemia.''; Leukemia, 2007 PubMed Europe PMC Scholia
  24. Scandura JM, Boccuni P, Cammenga J, Nimer SD; ''Transcription factor fusions in acute leukemia: variations on a theme.''; Oncogene, 2002 PubMed Europe PMC Scholia
  25. Martelli AM, Nyåkern M, Tabellini G, Bortul R, Tazzari PL, Evangelisti C, Cocco L; ''Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia.''; Leukemia, 2006 PubMed Europe PMC Scholia
  26. Mizuki M, Schwable J, Steur C, Choudhary C, Agrawal S, Sargin B, Steffen B, Matsumura I, Kanakura Y, Böhmer FD, Müller-Tidow C, Berdel WE, Serve H; ''Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations.''; Blood, 2003 PubMed Europe PMC Scholia
  27. Heo SK, Noh EK, Kim JY, Jeong YK, Jo JC, Choi Y, Koh S, Baek JH, Min YJ, Kim H; ''Targeting c-KIT (CD117) by dasatinib and radotinib promotes acute myeloid leukemia cell death.''; Sci Rep, 2017 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
135331view19:43, 23 August 2024Khanspersupdated lit ref
135330view19:42, 23 August 2024KhanspersModified description
135010view11:41, 31 July 2024EweitzRefine organelle membrane layering, refine legend
134962view11:44, 30 July 2024EweitzRefine state layering
134961view11:41, 30 July 2024EweitzStandardize case
134960view11:35, 30 July 2024EweitzIncrease interaction computability, economize layout
134959view11:22, 30 July 2024EweitzEconomize layout
134956view03:57, 30 July 2024EweitzEconomize layout
127508view17:43, 13 October 2023KhanspersOntology Term : 'bone cancer pathway' added !
127507view17:42, 13 October 2023KhanspersOntology Term : 'myeloid cell' added !
127506view17:41, 13 October 2023KhanspersOntology Term : 'bone marrow cancer' added !
127505view17:41, 13 October 2023KhanspersOntology Term : 'acute myeloid leukemia pathway' added !
127504view17:40, 13 October 2023KhanspersModified description
127503view17:25, 13 October 2023Khanspersupdated interactions and phosphosites
126561view23:51, 2 June 2023Khanspersadded GLI1
126560view22:01, 2 June 2023Khanspersupdate phosphosites
126559view21:31, 2 June 2023Khanspersadding phospho sites and updating interactions
126070view22:11, 31 March 2023Khanspersupdated JUP/TCF part, added phosphosite comments
126069view19:06, 31 March 2023KhanspersAdded nucleus, changed layout
126068view18:26, 31 March 2023Khansperswork in progress: updated literature for FLT3-ITD in ER
124513view00:47, 4 November 2022EweitzModified title
124512view21:42, 3 November 2022Khanspersadded FLT3 in ER
124450view00:22, 28 October 2022Khanspersadded therapies targeting FLT3
124449view00:03, 28 October 2022Khanspersupdate board size
124448view23:20, 27 October 2022Khanspersadded legend and therapies targeting KIT
124447view20:37, 27 October 2022KhanspersAdded stages
124446view20:09, 27 October 2022KhanspersAdded additional literature references
124445view18:56, 27 October 2022Khanspersadded literature references
124399view22:17, 25 October 2022KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKT1GeneProductENSG00000142208 (Ensembl)
AKT2GeneProductENSG00000105221 (Ensembl)
AKT3GeneProductENSG00000117020 (Ensembl)
ARAFGeneProduct369 (Entrez Gene)
Arsenic trioxideMetaboliteCHEBI:49900 (ChEBI)
BADGeneProductENSG00000002330 (Ensembl)
BCL2A1GeneProductENSG00000140379 (Ensembl)
BRAFGeneProductENSG00000157764 (Ensembl)
CCNA1GeneProductENSG00000133101 (Ensembl)
CCNA2GeneProductENSG00000145386 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl)
CD14GeneProductENSG00000170458 (Ensembl)
CEBPAGeneProductENSG00000245848 (Ensembl)
CEBPEGeneProductENSG00000092067 (Ensembl)
CHUKGeneProductENSG00000213341 (Ensembl)
CSF1RGeneProductENSG00000182578 (Ensembl)
CSF2GeneProductENSG00000164400 (Ensembl)
CrenolanibMetaboliteQ5184160 (Wikidata)
DUSP6GeneProductENSG00000139318 (Ensembl)
DasatinibMetaboliteCHEBI:49375 (ChEBI)
EIF4EBP1GeneProductENSG00000187840 (Ensembl)
EntospletinibMetaboliteQ27077193 (Wikidata)
FCGR1AGeneProductENSG00000150337 (Ensembl)
FLT3-ITD immature formGeneProductENSG00000122025 (Ensembl)
FLT3-ITDGeneProductENSG00000122025 (Ensembl)
FostamatinibMetaboliteQ5473550 (Wikidata)
GLI1GeneProduct2735 (Entrez Gene)
GRB2GeneProductENSG00000177885 (Ensembl)
GilteritinibMetaboliteQ27077802 (Wikidata)
HRASGeneProductENSG00000174775 (Ensembl)
IKBKBGeneProductENSG00000104365 (Ensembl)
IKBKGGeneProductENSG00000269335 (Ensembl)
IL3GeneProductENSG00000164399 (Ensembl)
ITGAMGeneProductENSG00000169896 (Ensembl)
IbrutinibMetaboliteCHEBI:76612 (ChEBI)
JUPGeneProductENSG00000173801 (Ensembl)
KITGeneProductENSG00000157404 (Ensembl)
KRASGeneProductENSG00000133703 (Ensembl)
LEF1GeneProductENSG00000138795 (Ensembl)
LestaurtinibMetaboliteQ6531771 (Wikidata)
MAP2K1GeneProduct5604 (Entrez Gene)
MAP2K2GeneProduct5605 (Entrez Gene)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MPOGeneProductENSG00000005381 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
MYCGeneProductENSG00000136997 (Ensembl)
MidostaurinMetaboliteCHEBI:63452 (ChEBI)
NFKB1GeneProductENSG00000109320 (Ensembl)
NRASGeneProductENSG00000213281 (Ensembl)
PER2GeneProductENSG00000132326 (Ensembl)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CBGeneProductENSG00000051382 (Ensembl)
PIK3CDGeneProductENSG00000171608 (Ensembl)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PIK3R2GeneProductENSG00000105647 (Ensembl)
PIK3R3GeneProductENSG00000117461 (Ensembl)
PIM1GeneProductENSG00000137193 (Ensembl)
PIM2GeneProductENSG00000102096 (Ensembl)
PIP3MetaboliteCHEBI:16618 (ChEBI)
PMLGeneProductENSG00000140464 (Ensembl)
PPARDGeneProductENSG00000112033 (Ensembl)
PonatinibMetaboliteCHEBI:78543 (ChEBI)
QuizartinibMetaboliteCHEBI:90217 (ChEBI)
RAF1GeneProductENSG00000132155 (Ensembl)
RARAGeneProductENSG00000131759 (Ensembl)
RELAGeneProduct5970 (Entrez Gene)
RPS6KB1GeneProductENSG00000108443 (Ensembl)
RPS6KB2GeneProductENSG00000175634 (Ensembl)
RUNX1GeneProductENSG00000159216 (Ensembl)
RUNX1T1GeneProductENSG00000079102 (Ensembl)
RadotinibMetaboliteQ15269680 (Wikidata)
Retinoic acidMetaboliteCHEBI:15367 (ChEBI)
SOS1GeneProductENSG00000115904 (Ensembl)
SOS2GeneProductENSG00000100485 (Ensembl)
SPI1GeneProductENSG00000066336 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl)
STAT5AGeneProductENSG00000126561 (Ensembl)
STAT5BGeneProductENSG00000173757 (Ensembl)
SorafenibMetaboliteCHEBI:50924 (ChEBI)
SunitinibMetaboliteCHEBI:38940 (ChEBI)
TCF7GeneProductENSG00000081059 (Ensembl)
TCF7L1GeneProductENSG00000152284 (Ensembl)
TCF7L2GeneProductENSG00000148737 (Ensembl)
ZBTB16GeneProductENSG00000109906 (Ensembl)

Annotated Interactions

No annotated interactions

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