Leukemia Under the Microscope

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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