Related Experiment Video

Updated: May 28, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

AMP-dependent kinase/mammalian target of rapamycin complex 1 signaling in T-cell acute lymphoblastic leukemia:

C Grimaldi1, F Chiarini, G Tabellini

  • 1Department of Human Anatomy, University of Bologna, Bologna, Italy.

Leukemia
|October 5, 2011
PubMed

Insights

Metformin, an activator of the LKB1/AMPK pathway, effectively combats T-cell acute lymphoblastic leukemia (T-ALL) by inhibiting mTORC1 signaling. This anti-diabetic drug shows significant anti-leukemic activity with reduced toxicity to healthy T-cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Mammalian target of rapamycin (mTOR) signaling is crucial for leukemic cell survival and proliferation.
  • The liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) pathway can downmodulate mTORC1 activity.
  • Metformin, an anti-diabetic drug, activates the LKB1/AMPK pathway.

Purpose of the Study:

  • To investigate the therapeutic potential of metformin against T-cell acute lymphoblastic leukemia (T-ALL).
  • To assess metformin's effects on T-ALL cell viability, apoptosis, and mRNA translation.
  • To evaluate metformin's impact on leukemia-initiating cell subpopulations.

Main Methods:

  • Treatment of T-ALL cell lines and primary patient samples with metformin.
  • Western blot analysis to assess mTORC1 downstream target phosphorylation.
  • Evaluation of mRNA translation inhibition and cell viability assays.
  • Assessment of toxicity against healthy T-lymphocytes.

Main Results:

  • Metformin reduced T-ALL cell viability by inducing autophagy and apoptosis.
  • Metformin treatment led to dephosphorylation of mTORC1 downstream targets.
  • Significant inhibition of mRNA translation was observed in metformin-treated T-ALL cells.
  • Metformin selectively targeted leukemia-initiating cells in patient samples.
  • Metformin exhibited lower toxicity towards healthy T-lymphocytes.

Conclusions:

  • Metformin demonstrates significant anti-leukemic activity in T-ALL.
  • Metformin's mechanism involves mTORC1 inhibition and mRNA translation suppression.
  • LKB1/AMPK activators, like metformin, represent promising therapeutic candidates for T-ALL treatment.

More Related Videos

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

Preparation of Primary Acute Lymphoblastic Leukemia Cells in Different Cell Cycle Phases by Centrifugal Elutriation09:09

Preparation of Primary Acute Lymphoblastic Leukemia Cells in Different Cell Cycle Phases by Centrifugal Elutriation

Published on: November 10, 2017

Related Concept Videos

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...
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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
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...
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...