Leukemia Under the Microscope

By AMBER HSIAO
Contributing Writer
Wednesday, November 2, 2005

In a recent study, UC Berkeley researchers were able to use bone marrow 
samples in order to analyze differences related to childhood leukemia. The 
marrow samples contain a shortened version of a protein that is observed at 
different levels of progression in children with leukemia. 
"The goal of the study was to find differences in proteins among various 
leukemia subtypes, which may be useful for clinical diagnosis or 
understanding how different leukemias develop," said Christine Hegedus, 
primary author of the paper and a post-doctoral fellow in the UC Berkeley 
Molecular Toxicology Program. 

Researchers initially examined cell lines, which are essentially 
immortalized cells that are isolated from the human body, and then 
manipulated for use in labs. When looking at these cell lines, many 
differences in proteins were found between leukemia subgroups. A shorter 
version of the protein called ubiquitin was found having greater levels in 
some leukemia subgroups versus others. 

"This protein is crucial to many cellular functions and finding a difference 
in levels of a shortened version of the protein was extremely interesting," 
Hegedus said. "Therefore, we wanted to see if this difference is also seen 
in samples taken from children with leukemia." 

Researchers wanted to better understand ubiquitin by examining bone marrow 
from leukemia patients. They collaborated with the Northern California 
Childhood Leukemia Study at UC Berkeley to collect bone marrow samples from 
children who had been recently diagnosed with leukemia. 

"Again, there were many differences in proteins among the groups of 
leukemias and we did see a difference in a protein that may be the shortened 
ubiquitin," Hegedus said. "We are currently conducting follow-up studies to 
determine the identities of the bone marrow proteins, including the one that 
may be ubiquitin." 

In order to examine the bone marrow samples, researchers used surface-
enhanced laser desportion and ionization time-of-flight mass spectrometry. 
By using this technology, scientists can then look at the majority of 
proteins present in a sample at any one time. 

These protein samples are prepared by first placing them on a surface that 
allows the proteins to adhere based on their biochemical properties. When 
laser energy is applied to this surface, the proteins detach and travel down 
a time-of-flight tube. The time that the protein takes to travel down this 
path allows researchers to determine the mass of the protein. 

"Using this technology, we were able to compare the proteins in the 
different leukemias," Hegedus said. 

The leukemia subtypes are broken down based on cell lineage and level of 
cellular differentiation. Researchers also use proteome analysis, a way to 
analyze all the proteins present in the bond marrow cells at any given time. 

"Instead of looking at one or two proteins, we are looking at all or a 
majority of the proteins in the cells at one time," Hegedus said. "This 
allows us to quickly screen for differences in proteins which we can later 
identify. 

The main types of leukemia include acute lymphoblastic leukemia, acute 
myeloid leukemia, chronic lymphocytic leukemia and chronic myelogenous 
leukemia. Further studies are still needed to determine the significance of 
the different levels of the truncated ubiquitin. 

"Ubiquitin itself is important in many cellular processes such as growth and 
differentiation," Hegedus said. "Most commonly, it acts as a tag on a 
protein to target that protein for degradation. Therefore, a shortened 
version that is present at varying levels may affect degradation of target 
proteins leading to a variety of defects." 

These findings may pave the way for future research on childhood leukemia. 

"Our results may open new doors for research by providing specific target 
protein for research on how these diseases develop or how to treat them," 
Hegedus said. "Hopefully our study will drive the development of this and 
new technologies for cancer research."





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