Hematopoietic progenitors

Hematopoietic cell lineage

PIP3
mTOR

Jak-STAT Signaling

Acute myeloblastic leukemia with minimal differentiation (MO)

Protein Synthesis

Cell Survival

Acute myeloblastic leukemia without maturation (M1) Acute myeloblastic leukemia with maturation (M2) Acute promyelocytic leukemia (M3) Acute myelomonocytic leukemia(M4) Acute myelomonocytic leukemia with abnormal eosinophils (M4Eo) Acute monocytic leukemia (M5) Erythroleukemia (M6) Acute megakaryocytic leukemia (M7) Genetic alterations Oncogenes: c-KIT, FLT3, N- or K-Ras, AML1-ETO, PML-RAR, PLZF-RAR Tumor suppressors: AML1, C/EBP, PU.1

DNA DNA DNA

DNA Anti-apoptotic genes

DNA DNA PU.1 target genes

DNA C/EBP target genes

DNA AML 1 targets genes

Proliferation

Block of differentiation

Anti-apoptosis

Acute Myeloid Leukemia Signaling Pathway

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.

4EBP1 / EIF4EBP1 65030-1-Ig Mouse mono ELISA, WB, IHC

JUP 11146-1-AP Rabbit poly ELISA, WB, IHC

c-KIT 18696-1-AP Rabbit poly ELISA, WB, IHC

STAT3 51076-2-AP Rabbit poly ELISA, WB, IHC

c-Myc 10828-1-AP Rabbit poly ELISA, WB, IHC

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HRAS (Ras) 18295-1-AP Rabbit poly ELISA, WB, IHC S6K1 / p70(S6K) 14485-1-AP Rabbit poly ELISA, WB, IHC