Related Experiment Video

Updated: Aug 11, 2026

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
10:21

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Published on: February 21, 2018

Hyperactivation of the RAS signaling pathway in myelodysplastic syndrome with AML1/RUNX1 point mutations

H Niimi1, H Harada, Y Harada

  • 1Department of Hematology/Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.

Leukemia
|February 10, 2006
PubMed

Insights

Mutations in AML1/RUNX1 are linked to specific genetic changes like -7/7q- and increased receptor tyrosine kinase-RAS pathway activation in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). These findings clarify distinct molecular pathways in MDS/AML development.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Mutations in AML1/RUNX1 are frequently observed in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) developing from MDS (MDS/AML).
  • While AML1 mutations are implicated in MDS/AML pathogenesis, additional genetic alterations are crucial for disease development.

Purpose of the Study:

  • To investigate and compare gene alterations in MDS/AML patients with and without AML1 mutations.
  • To identify specific genetic alterations and signaling pathway involvement associated with AML1 mutations in MDS/AML.

Main Methods:

  • Comparative analysis of gene alterations in MDS/AML patients stratified by the presence or absence of AML1 mutations.
  • Assessment of chromosomal abnormalities, including -7/7q- and -5/5q-.
  • Mutation analysis of key genes in signaling pathways, including FLT3, N-RAS, PTPN11, NF1, and p53.
  • Evaluation of surface marker expression (c-KIT) and downstream signaling (ERK activation) in relation to specific mutations.

Main Results:

  • AML1 mutations were significantly associated with the chromosomal alteration -7/7q-.
  • MDS/AML patients without AML1 mutations frequently exhibited -5/5q- and complex karyotypes.
  • A higher frequency of mutations in FLT3, N-RAS, PTPN11, and NF1 genes was observed in AML1-mutated patients, leading to increased activation of receptor tyrosine kinase (RTK)-RAS signaling pathways (38% vs. 6.3%).
  • p53 mutations were exclusively found in patients without AML1 mutations.
  • AML1-mutated cells expressed c-KIT and demonstrated enhanced ERK activation upon stem cell factor stimulation.

Conclusions:

  • MDS/AML associated with AML1/RUNX1 mutations shows a distinct genetic profile, characterized by -7/7q- and frequent activation of the RTK-RAS signaling pathway.
  • These findings highlight distinct molecular mechanisms underlying MDS/AML based on AML1 mutation status.
  • Understanding these differences can inform targeted therapeutic strategies for MDS/AML patients.

More Related Videos

Identifying Bone Marrow Microenvironmental Populations in Myelodysplastic Syndrome and Acute Myeloid Leukemia06:33

Identifying Bone Marrow Microenvironmental Populations in Myelodysplastic Syndrome and Acute Myeloid Leukemia

Published on: November 10, 2023

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...