Finding the origins of infant leukaemia
Leukaemia arises as a result of genetic or epigenetic alterations in blood cells, leading to an aberrant accumulation of undifferentiated blasts. Understanding the molecular pathogenesis and aetiology of infant leukaemia induced by the MLL-AF4 fusion gene was the subject of the Leukaemogenesis project.
The mixed lineage leukaemia (MLL) gene is one of the most frequently mutated genes in infant acute leukaemias, leading to fusions that involve more than 50 different partners. Detection of MLL translocations at diagnosis is a strong negative prognostic marker of the disease.
In infant acute lymphoblastic leukaemia (ALL), MLL-AF4 is very common and arises in utero. However, very little is known about the nature of the target cell that becomes transformed in the embryo and the mechanisms accounting for its B cell lineage affiliation.
Although various murine models for MLL leukaemias exist, they fail to replicate many of the features of the human disease, suggesting that there are essential steps during early human development required for leukaemia onset. Seeking to address this issue, the EU Leukaemogenesis project was designed to determine the cell population that was most vulnerable to transformation by the MLL-AF4 gene.
As a first approach, scientists explored the in vitro and in vivo developmental impact of MLL-AF4 expression on haematopoietic stem progenitor cells (HSPCs) isolated from umbilical cord blood. MLL-AF4 seemed to augment the proliferation, clonogenic potential and in vivo multilineage haematopoietic engraftment of HSPCs. However, it was not sufficient to induce leukaemogenesis on its own, indicating that either additional hits were required to develop leukaemia or these cells were the inappropriate target.
In a similar way, MLL-AF4 expression was not sufficient to transform haematopoietic cells differentiated from human embryonic stem cells (hESC). Interestingly, a reduced production of haematopoietic cells was observed concomitant with an enhanced mature endothelial cell fate, suggesting that MLL-AF4 skewed the potential of common haemato-endothelial precursors towards a pronounced endothelial cell fate.
Scientists are hopeful that the precise mechanism of MLL-AF4–mediated cell transformation would be addressed by studying induced pluripotent stem cells (iPSCs) from infant patient blasts. Nonetheless, the platform generated during the Leukaemogenesis project constitutes an important tool for studying cellular and molecular mechanisms during early embryonic development and could be further utilised for drug screening and toxicity.
Provided by CORDIS
- Tracking the molecular pathway to mixed-lineage leukemia Dec 15, 2008 | not rated yet | 0
- Mouse model highlights histone methylation as distinguishing feature for leukemia subtypes Nov 03, 2008 | not rated yet | 0
- Stem cell treatment to prevent leukemia returning is a step closer, say scientists Jun 02, 2011 | not rated yet | 0
- Unique role for blood formation gene identified Sep 12, 2007 | not rated yet | 0
- Tackling a hard-to-treat childhood cancer by targeting epigenetic changes Nov 03, 2008 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
Older prostate cancer patients with other underlying health conditions should think twice before committing to surgery or radiation therapy for their cancer, according to a multicenter study led by researchers in the UCLA ...
Cancer 12 hours ago | not rated yet | 0 |
Intensity-modulated radiation therapy has become the most commonly used type of radiation in prostate cancer, but research from the University of North Carolina suggests that the therapy may not be more effective than older, ...
Cancer 14 hours ago | not rated yet | 0
New research suggests that a compound abundant in the Mediterranean diet takes away cancer cells' "superpower" to escape death. By altering a very specific step in gene regulation, this compound essentially re-educates cancer ...
Cancer 15 hours ago | 4.8 / 5 (12) | 2 |
(HealthDay)—For young adults needing either a chest or abdominopelvic computed tomography (CT), the short-term risk of death from underlying morbidity is greater than the long-term risk of radiation-induced ...
Cancer 16 hours ago | not rated yet | 0
In a new study described in the journal Oncogene, researchers reveal how a key player in cell growth, immunity and the inflammatory response can be transformed into a primary contributor to tumor growth.
Cancer 21 hours ago | not rated yet | 0 |
(Medical Xpress)—Cardiologists have identified a trio of biomarkers that may predict which patients with heart disease have a high risk of heart attack or death in the next two years.
14 minutes ago | not rated yet | 0 |
Each day, an average of nine people are killed in the United States and more than 1,000 injured by drivers doing something other than driving.
29 minutes ago | not rated yet | 0
(Medical Xpress)—We spend about a third of our life asleep, but why we need to do so remains a mystery. In a recent publication, researchers at University of Surrey and University College London suggest a new hypothesis, ...
24 minutes ago | not rated yet | 0
(Medical Xpress)—International researchers are studying the salt intake of Indian adults to provide vital new data to aid the development of a national salt reduction strategy.
14 minutes ago | not rated yet | 0
(Medical Xpress)—Exposure to sunshine as a small child is crucial to the development of a healthy eye according to results of long-term myopia study conducted by University of Sydney researchers.
4 minutes ago | not rated yet | 0