A new technique to study how myeloids become white blood cells
University of Illinois cell and developmental Biology professor Fei Wang and colleagues have created a new technique to study how myeloids, a type of blood stem cell, become the white blood cells important for immune system defense against infections and tissue damage. This approach offers new insights into the molecular mechanisms at work during myeloid differentiation, and may improve our ability to treat myeloid diseases like leukemia, the researchers report. Their findings appear in the journal Blood.
Myeloids are blood stem cells from bone marrow or the spinal cord that differentiate into common types of white blood cells like neutrophils and macrophages. Deficiencies in this differentiation process can cause leukemia.
Researchers in the field had previously studied myeloid differentiation by using cells taken directly from animals, or they transformed leukemia tumor cells to their previous myeloid stem cell-like states. Primary cells are hard to grow and manipulate genetically, however, and tumor cells still contain the genetic mutations that caused them to divide uncontrollably in the first place. The drawbacks of these systems prompted Wang to develop a better method for studying the mechanisms of myeloid differentiation.
Wang and his team began by turning mouse embryonic stem cells into myeloid progenitor cells. They then added a protein called Hoxb8 to these cells that had been shown previously to immortalize myeloid progenitor cells.
"This really simplified the whole system, so, number one, we didn't have to deal with animals or human bodies, and, number two, we immortalized these cells so that they can be easily handled in culture and maintain normal myeloid progenitor cell genetic information," Wang said.
The researchers wanted to prove that their model is effective in helping them determine the molecular mechanisms important to myeloid differentiation, so they turned to a class of enzymes, called protein kinases, that are known to mediate processes like cell development, immune response, and cell differentiation. The researchers screened a variety of protein kinase inhibitors to find potential key regulators of myeloid differentiation.
A protein kinase inhibitor of a molecule called mTor, a master regulator of cell behavior, was found to interfere with myeloid differentiation, signifying that mTor is a key regulator of this process. Further experiments showed that this molecule is necessary for myeloid differentiation.
"This is the first evidence showing that this molecule plays a significant role in myeloid differentiation," Wang said.
This finding serves as a proof of principle that the new approach provides a powerful tool for future studies of normal and abnormal myeloid differentiation, Wang said.
"Using this system, we can introduce genetic manipulations that tell us something very important about how normal myeloid differentiation works, and what kind of molecular events in this process can go wrong, leading to diseases like leukemia," Wang said.
"People can use this as a platform for large-scale screening analysis for drugs that potentially can promote myeloid differentiation and can slow down or stop myeloid disease processes."
More information: Blood bloodjournal.hemat… 979.abstract
Journal reference: Blood
Provided by University of Illinois at Urbana-Champaign
- A new target in acute myeloid leukemia Jul 16, 2012 | not rated yet | 0
- Insulin, nutrition prevent blood stem cell differentiation in fruit flies Mar 12, 2012 | not rated yet | 0
- Leukemia stem cells have more in common with embryonic stem cells than adult stem cells Feb 05, 2009 | not rated yet | 0
- Study reveals origins of a cancer affecting the blood and bone marrow May 12, 2011 | not rated yet | 0
- Regulating hematopoietic differentiation Oct 05, 2012 | 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
The use of a smartphone application significantly improves patients' preparation for a colonoscopy, according to new research presented today at Digestive Disease Week (DDW). The preparation process, which begins days in ...
Cancer 9 hours ago | not rated yet | 0
Research presented at Digestive Disease Week (DDW) explores new methods for managing digestive health through diet and lifestyle.
Cancer 9 hours ago | not rated yet | 1
A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...
Cancer May 18, 2013 | 5 / 5 (2) | 0
(HealthDay)—Concurrent use of two immune checkpoint antibodies—ipilimumab and nivolumab—may be effective for the treatment of advanced melanoma, according to a proof-of-principal study presented in ...
Cancer May 17, 2013 | not rated yet | 0
(HealthDay)—The risks of metastasis and death associated with cutaneous squamous cell carcinoma (CSCC) are low, but significant, and risk factors for poor outcome include tumor diameter, invasion beyond ...
Cancer May 17, 2013 | not rated yet | 0 |
The devastating effect of Alzheimer's disease on bilingual people has been thrown into focus in Canada, where the sudden loss of a second language can leave sufferers feeling like strangers in their own country.
33 minutes ago | not rated yet | 0
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
2 hours ago | not rated yet | 0
Regular consumption of coffee is associated with a reduced risk of primary sclerosing cholangitis (PSC), an autoimmune liver disease, Mayo Clinic research shows. The findings were being presented at the Digestive Disease ...
10 hours ago | not rated yet | 0 |
Patients with treatment-resistant major depression saw dramatic improvement in their illness after treatment with ketamine, an anesthetic, according to the largest ketamine clinical trial to-date led by researchers from the ...
10 hours ago | 4.7 / 5 (3) | 0 |
There are significant cost and risk factors associated with two procedures commonly used to diagnose or treat gastrointestinal problems, according to research presented at Digestive Disease Week (DDW).
9 hours ago | not rated yet | 0