KIT in AML

Pathway ID: SIGNOR-AML-KIT

Description: The Class III tyrosine kinase, Stem Cell factor receptor/c-Kit, plays a critical role in hematopoiesis. The Ras/Erk, JAK/STAT and the PI3-kinase/AKT pathways are the key signaling pathways involved in the regulation of cell proliferation, survival, and differentiation induced by c-Kit. KIT activation/gain of function mutations occur in 60-80% of Acute Myeloid Leukemia (AML) patients and in 12.8-46.1% of adults with Core Binding factor (CBF) leukemia. AML chromosomal abnormalities form different subgroups. The AML with fused transcripts such as RUNX1-RUNX1T1 t(8;21)(q22;q22) or CBFbeta-MYH11 inv(16)(p13;q22) form the group Core Binding Factor-AML (CBF-AML). Numerous studies suggest that c-kit mutations could have effects on the relapse and white blood cell increase in CBF-AML adults, expecially in patients with t(8,21). The gain-of-function mutations in the oncogene KIT can transform by different mechanisms, such as: Impair apoptosis (e.g.,by inhibitory phosphorylation of BAD) or induce growth and survival in a ligand independent/altered substrate specificity way. Moreover, a lowered degree of cell surface expression of receptor onco-mutants has been described. The PTPN11 gene encodes the human SHP2 non-receptor tyrosine phosphatase (chr. 12q24), which positively participates in signal events downstream of growth factors receptors and plays a key role in the proliferation and survival of hematopoietic cells. PTPN11 mutations and mutations in FLT3/ITD, KIT, KRAS or CEBPA seem to be mutually exclusive. PMID: 19265199, 27613372, 17972951

Curated by: irozzo

33 Seed Entities

Organism:
Name Primary ID
BCL2 P10415
MEK1/2 SIGNOR-PF25
KITLG P21583
RUNX1 Q01196
MTOR P42345
GRB2 P62993
BCL2L1 Q07817
STAT5A P42229
MYC P01106
STAT3 P40763
PI3K SIGNOR-C156
PDPK1 O15530
SH2B3 Q9UQQ2
Differentiation SIGNOR-PH37
CBFbeta-MYH11 SIGNOR-FP3
CUX1 P39880
PTPN11 Q06124
CBLB Q13191
NRAS P01111
JAK2 O60674
KIT P10721
BRAF P15056
PIP3 CHEBI:16618
PIK3IP1 Q96FE7
Apoptosis SIGNOR-PH2
ETV6 P41212
Proliferation SIGNOR-PH4
CDK1 P06493
ERK1/2 SIGNOR-PF1
CBL P22681
TP53 P04637
SOS1 Q07889
AKT SIGNOR-PF24