Acute myeloid leukemia (Homo sapiens)

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1, 5, 6, 9, 10, 12...1124131447819233ERNucleusM3: Acute promyelocytic leukemiaM0M4: Acute myelomonocytic leukemiaM7: Acute megakaryotic leukemiaM0: Acute myeloblastic leukemia with minimal differentiationM2: Acute myeloblastic leukemia with maturationLegendProliferative genesM6: ErythroleukemiaProliferationM1: Acute myeloblastic leukemia without maturationActivating mutationAML-ETOM5: Acute monocytic leukemiaRETINOIC ACIDKITmidostaurinArsenic trioxideRUNX1PIM1dasatinibGLI1FLT3-ITD1812, 1517, 20, 22GRB2SOS1SOS2HRASKRASNRASARAFRAF1PPBRAFPSTAT3STAT5ASTAT5BPIK3CAPIK3CBPIK3CDPIK3R1PIK3R2PIK3R3PIP3AKT1PPAKT2PAKT3PPCHUKIKBKBPPPIKBKGBADPPMTORPPNFKB1RELAPMAP2K1PPPMAPK1PPMAPK3PPMAP2K2PPEIF4EBP1RPS6KB1PPPPPRPS6KB2PPIM2BCL2A1CEBPESPI1RUNX1T1RUNX1PMLRARARARAZBTB16Anti-apoptotic genesProtein synthesisCell survivalAnti-apoptosisCEBPACEBPA2JUP4CCND14MYCPPARDDUSP6MYCCCNA2CCNA1PML-RARalphaPLZF-RARalphaLEF1TCF7TCF7L2TCF7L1CD14FCGR1AITGAMSPI127CSF1RPER2CEBPA targetgenes21CSF1RCSF2MPOIL3ProliferationBlock of differentiationBlock of differentiationProliferationRETINOIC ACID7M2M4M1, 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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History

View all...
CompareRevisionActionTimeUserComment
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)
DUSP6GeneProductENSG00000139318 (Ensembl)
EIF4EBP1GeneProductENSG00000187840 (Ensembl)
FCGR1AGeneProductENSG00000150337 (Ensembl)
FLT3-ITD immature formGeneProductENSG00000122025 (Ensembl)
FLT3-ITDGeneProductENSG00000122025 (Ensembl)
GLI1GeneProduct2735 (Entrez Gene)
GRB2GeneProductENSG00000177885 (Ensembl)
HRASGeneProductENSG00000174775 (Ensembl)
IKBKBGeneProductENSG00000104365 (Ensembl)
IKBKGGeneProductENSG00000269335 (Ensembl)
IL3GeneProductENSG00000164399 (Ensembl)
ITGAMGeneProductENSG00000169896 (Ensembl)
JUPGeneProductENSG00000173801 (Ensembl)
KITGeneProductENSG00000157404 (Ensembl)
KRASGeneProductENSG00000133703 (Ensembl)
LEF1GeneProductENSG00000138795 (Ensembl)
MAP2K1GeneProduct5604 (Entrez Gene)
MAP2K2GeneProduct5605 (Entrez Gene)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MPOGeneProductENSG00000005381 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
MYCGeneProductENSG00000136997 (Ensembl)
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)
RAF1GeneProductENSG00000132155 (Ensembl)
RARAGeneProductENSG00000131759 (Ensembl)
RELAGeneProduct5970 (Entrez Gene)
RETINOIC ACIDMetaboliteCHEBI:15367 (ChEBI)
RPS6KB1GeneProductENSG00000108443 (Ensembl)
RPS6KB2GeneProductENSG00000175634 (Ensembl)
RUNX1GeneProductENSG00000159216 (Ensembl)
RUNX1T1GeneProductENSG00000079102 (Ensembl)
SOS1GeneProductENSG00000115904 (Ensembl)
SOS2GeneProductENSG00000100485 (Ensembl)
SPI1GeneProductENSG00000066336 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl)
STAT5AGeneProductENSG00000126561 (Ensembl)
STAT5BGeneProductENSG00000173757 (Ensembl)
TCF7GeneProductENSG00000081059 (Ensembl)
TCF7L1GeneProductENSG00000152284 (Ensembl)
TCF7L2GeneProductENSG00000148737 (Ensembl)
ZBTB16GeneProductENSG00000109906 (Ensembl)
crenolanibMetaboliteQ5184160 (Wikidata)
dasatinibMetaboliteCHEBI:49375 (ChEBI)
entospletinibMetaboliteQ27077193 (Wikidata)
fostamatinibMetaboliteQ5473550 (Wikidata)
gilteritinibMetaboliteQ27077802 (Wikidata)
ibrutinibMetaboliteCHEBI:76612 (ChEBI)
lestaurtinibMetaboliteQ6531771 (Wikidata)
midostaurinMetaboliteCHEBI:63452 (ChEBI)
ponatinibMetaboliteCHEBI:78543 (ChEBI)
quizartinibMetaboliteCHEBI:90217 (ChEBI)
radotinibMetaboliteQ15269680 (Wikidata)
sorafenibMetaboliteCHEBI:50924 (ChEBI)
sunitinibMetaboliteCHEBI:38940 (ChEBI)

Annotated Interactions

No annotated interactions

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