A new technique to study how myeloids become white blood cells

October 25, 2012

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 like 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 to their previous myeloid stem cell-like states. are hard to grow and manipulate genetically, however, and tumor cells still contain the 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 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 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."

Explore further: A new target in acute myeloid leukemia

More information: Blood bloodjournal.hematologylibrary … 2-03-414979.abstract

Related Stories

A new target in acute myeloid leukemia

July 16, 2012
Acute myeloid leukemia, a common leukemia in adults, is characterized by aberrant proliferation of cancerous bone marrow cells. Activating mutations in a protein receptor known as FLT3 receptor are among the most prevalent ...

Study reveals origins of a cancer affecting the blood and bone marrow

May 12, 2011
A new study by the NYU Cancer Institute, an NCI-designated cancer center, sheds light on the origins of myeloid leukemia, a type of blood cancer that affects children and adults. The researchers discovered that novel mutations ...

Two-faced leukemia?

December 12, 2011
One kind of leukemia sometimes masquerades as another, according to a study published online this week in the Journal of Experimental Medicine.

Recommended for you

'Labyrinth' chip could help monitor aggressive cancer stem cells

September 21, 2017
Inspired by the Labyrinth of Greek mythology, a new chip etched with fluid channels sends blood samples through a hydrodynamic maze to separate out rare circulating cancer cells into a relatively clean stream for analysis. ...

Drug combination may improve impact of immunotherapy in head and neck cancer

September 21, 2017
Checkpoint inhibitor-based immunotherapy has been shown to be very effective in recurrent and metastatic head and neck cancer but only in a minority of patients. University of California San Diego School of Medicine researchers ...

Whole food diet may help prevent colon cancer, other chronic conditions

September 21, 2017
A diet that includes plenty of colorful vegetables and fruits may contain compounds that can stop colon cancer and inflammatory bowel diseases in pigs, according to an international team of researchers. Understanding how ...

New kinase detection method helps identify targets for developing cancer drugs

September 21, 2017
Purdue University researchers have developed a high-throughput method for matching kinases to the proteins they phosphorylate, speeding the ability to identify multiple potential cancer drug targets.

Poliovirus therapy induces immune responses against cancer

September 20, 2017
An investigational therapy using modified poliovirus to attack cancer tumors appears to unleash the body's own capacity to fight malignancies by activating an inflammation process that counter's the ability of cancer cells ...

Brain cancer growth halted by absence of protein, study finds

September 20, 2017
The growth of certain aggressive brain tumors can be halted by cutting off their access to a signaling molecule produced by the brain's nerve cells, according to a new study by researchers at the Stanford University School ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.