KEGG PATHWAY: hsa05221

PATHWAY: hsa05221

Entry

hsa05221 Pathway

Name

Acute myeloid leukemia - Homo sapiens (human)

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 AML-ETO, PML-RARalpha or PLZF-RARalpha block myeloid cell differentiation by repressing target genes. In other cases, the transcription factors themselves are mutated.

Class

Human Diseases; Cancers

Pathway map

hsa05221

Acute myeloid leukemia

Disease

H00003

Acute myeloid leukemia (AML)

Organism

Homo sapiens (human) [GN:hsa]

Gene

3815	KIT; v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog [KO:K05091] [EC:2.7.10.1]
2322	FLT3; fms-related tyrosine kinase 3 [KO:K05092] [EC:2.7.10.1]
5290	PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293	PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291	PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294	PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295	PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533	PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296	PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503	PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
207	AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208	AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000	AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
1147	CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551	IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
8517	IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
4790	NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970	RELA; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
572	BAD; BCL2-associated agonist of cell death [KO:K02158]
2475	MTOR; mechanistic target of rapamycin (serine/threonine kinase) [KO:K07203]
1978	EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205]
6198	RPS6KB1; ribosomal protein S6 kinase, 70kDa, polypeptide 1 [KO:K04688] [EC:2.7.11.1]
6199	RPS6KB2; ribosomal protein S6 kinase, 70kDa, polypeptide 2 [KO:K04688] [EC:2.7.11.1]
2885	GRB2; growth factor receptor-bound protein 2 [KO:K04364]
6654	SOS1; son of sevenless homolog 1 (Drosophila) [KO:K03099]
6655	SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
3265	HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog [KO:K02833]
4893	NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
3845	KRAS; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
369	ARAF; v-raf murine sarcoma 3611 viral oncogene homolog [KO:K08845] [EC:2.7.11.1]
673	BRAF; v-raf murine sarcoma viral oncogene homolog B1 [KO:K04365] [EC:2.7.11.1]
5894	RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [KO:K04366] [EC:2.7.11.1]
5604	MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605	MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594	MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595	MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6774	STAT3; signal transducer and activator of transcription 3 (acute-phase response factor) [KO:K04692]
6776	STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
6777	STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
5292	PIM1; pim-1 oncogene [KO:K04702] [EC:2.7.11.1]
11040	PIM2; pim-2 oncogene [KO:K08806] [EC:2.7.11.1]
861	RUNX1; runt-related transcription factor 1 [KO:K08367]
862	RUNX1T1; runt-related transcription factor 1 [KO:K10053]
5371	PML; promyelocytic leukemia [KO:K10054]
5914	RARA; retinoic acid receptor, alpha [KO:K08527]
7704	ZBTB16; zinc finger and BTB domain containing 16 [KO:K10055]
1050	CEBPA; CCAAT/enhancer binding protein (C/EBP), alpha [KO:K09055]
6688	SPI1; spleen focus forming virus (SFFV) proviral integration oncogene spi1 [KO:K09438]
3728	JUP; junction plakoglobin [KO:K10056]
6932	TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
83439	TCF7L1; transcription factor 7-like 1 (T-cell specific, HMG-box) [KO:K04490]
6934	TCF7L2; transcription factor 7-like 2 (T-cell specific, HMG-box) [KO:K04491]
51176	LEF1; lymphoid enhancer-binding factor 1 [KO:K04492]
595	CCND1; cyclin D1 [KO:K04503]
4609	MYC; v-myc myelocytomatosis viral oncogene homolog (avian) [KO:K04377]
5467	PPARD; peroxisome proliferator-activated receptor delta [KO:K04504]
8900	CCNA1; cyclin A1 [KO:K06627]

Compound

C05981

Phosphatidylinositol-3,4,5-trisphosphate

Reference

PMID:16236521

Authors

Steffen B, Muller-Tidow C, Schwable J, Berdel WE, Serve H.

Title

The molecular pathogenesis of acute myeloid leukemia.

Journal

Crit Rev Oncol Hematol 56:195-221 (2005)

Reference

PMID:12563308

Authors

Tenen DG.

Title

Disruption of differentiation in human cancer: AML shows the way.

Journal

Nat Rev Cancer 3:89-101 (2003)

Reference

PMID:16146838

Authors

Choudhary C, Muller-Tidow C, Berdel WE, Serve H.

Title

Signal transduction of oncogenic Flt3.

Journal

Int J Hematol 82:93-9 (2005)

Reference

PMID:12951584

Authors

Stirewalt DL, Radich JP.

Title

The role of FLT3 in haematopoietic malignancies.

Journal

Nat Rev Cancer 3:650-65 (2003)

Reference

PMID:16642045

Authors

Martelli AM, Nyakern M, Tabellini G, Bortul R, Tazzari PL, Evangelisti C, Cocco L.

Title

Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia.

Journal

Leukemia 20:911-28 (2006)

Reference

PMID:15625120

Authors

Lennartsson J, Jelacic T, Linnekin D, Shivakrupa R.

Title

Normal and oncogenic forms of the receptor tyrosine kinase kit.

Journal

Stem Cells 23:16-43 (2005)

Reference

PMID:11721960

Authors

Lorsbach RB, Downing JR.

Title

The role of the AML1 transcription factor in leukemogenesis.

Journal

Int J Hematol 74:258-65 (2001)

Reference

PMID:12468433

Authors

Mizuki M, Schwable J, Steur C, Choudhary C, Agrawal S, Sargin B, Steffen B, Matsumura I, Kanakura Y, Bohmer FD, Muller-Tidow C, Berdel WE, Serve H.

Title

Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations.

Journal

Blood 101:3164-73 (2003)

Reference

PMID:17554387

Authors

Mikesch JH, Steffen B, Berdel WE, Serve H, Muller-Tidow C.

Title

The emerging role of Wnt signaling in the pathogenesis of acute myeloid leukemia.

Journal

Leukemia : (2007)

Reference

PMID:16352814

Authors

Mueller BU, Pabst T, Fos J, Petkovic V, Fey MF, Asou N, Buergi U, Tenen DG.

Title

ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression.

Journal

Blood 107:3330-8 (2006)

KO pathway

ko05221

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Ontology (3)   
   KEGG BRITE (3)   
Pathway (1)   
   BioSystems (1)   
Disease (1)   
   KEGG DISEASE (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (57)   
   KEGG GENES (57)   
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