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Two major types of genetic event are crucial for the molecular pathogenesis of acute myeloid leukemias (AML): activating mutations of signal transduction intermediates and alterations in myeloid transcription factors governing hematopoietic differentiation. Both aberrant and constitutive activation of signal transduction molecules are found in about 50% of primary AML bone marrow samples, and seem to contribute to the increased proliferation and apoptosis resistance. The most common of these activating events were observed in the FLT3, in N-Ras and K-Ras and in Kit. Specific haematopoietic transcription factors are crucial for differentiation to particular lineages during normal differentiation, but are frequently disrupted in AML. Some mechanisms of disruption involve the effect of fusion proteins that are generated by chromosomal translocations on haematopoietic transcription factors. In other cases, the transcription factors themselves are mutated.
Acute Myeloid LeukemiaSignaling Pathway
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18696-1-AP
ELISA, WB, IHC
HRAS (Ras)
18295-1-AP
Rabbit poly
ELISA, WB, IHC
S6K1 / p70(S6K) 14485-1-AP Rabbit poly ELISA, WB, IHC
65030-1-Ig
Mouse mono
ELISA, WB, IHC
PIP3
CellSurvival
ProteinSynthesis
Block of differentiation
Anti-apoptotic genes
DNA
Proliferation
DNA
DNA DNA
DNA
DNA
DNA
DNA
Jak-STATSignaling
AML 1targetsgenes
C/EBPαtargetgenes
PU.1targetgenes
Anti-apoptosis
Genetic alterations
Oncogenes:c-KIT, FLT3, N- or K-Ras, AML1-ETO, PML-RARα, PLZF-RARα
Tumor suppressors:AML1, C/EBPα, PU.1
Hematopoietic progenitors
Acute myeloblastic leukemia with minimal differentiation (MO)
Acute myeloblastic leukemia without maturation (M1)
Acute myeloblastic leukemia with maturation (M2)
Acute promyelocytic leukemia (M3)
Acute myelomonocytic leukemia(M4)
Acute myelomonocytic leuke-mia with abnormal eosinophils (M4Eo)
Acute monocytic leukemia (M5)
Erythroleukemia (M6)
Acute megakaryocytic leuke-mia (M7)
Hematopoieticcell lineage
mTOR
c-Myc
10828-1-AP
Rabbit poly
ELISA, WB, IHC
4EBP1 / EIF4EBP1
c-KIT
Rabbit poly
JUP
11146-1-AP
Rabbit poly
ELISA, WB, IHC
STAT3
51076-2-AP
Rabbit poly
ELISA, WB, IHC