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Personalizing Leukemia Treatment
Researchers are revealing how cytokines and chemokines affect protein expression.!--h2>
Steven Kornblau, M.D., has been on the faculty at MD Anderson Cancer Center in Houston, Texas, for 20 years, where he divides his time between research into understanding leukemia and a clinical practice where he treats patients with the disease.
“Leukemic cells don’t live in isolation; they’re interacting with their environment within the bone marrow—they’re interacting with their environment in terms of the blood that flows by them,” says Dr. Kornblau.
Today, his research is revealing how the cytokines and chemokines that leukemic cells might be getting exposed to affect protein expression. The idea that researchers in his lab might find different cytokine and chemokine expression patterns within leukemic cells led to determining ways of profiling large numbers of cytokines.
Researchers in Dr. Kornblau’s lab considered using ELISA kits for the chemokine and cytokine studies, but determined that this approach would require a significant amount of sample. There was also concern about the impact of batch effects on results.
“We were looking for something where we could analyze a lot of cytokines and chemokines simultaneously that also wouldn’t require too much material,” says Dr. Kornblau. “Around that time we saw that Bio-Rad was creating large cytokine kits, where you could look at numerous chemokines and cytokines simultaneously.”
The lab used the Bio-Plex Pro™ human cytokine 27-plex assay to study a large panel of serum samples from acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) patients (178 AML and 114 MDS samples). Because MDS is often considered to be “preleukemia,” one of the questions to be addressed was whether MDS and AML exhibit similar or unique cytokine patterns.
“The first thing we found was that for both diseases, the pattern of expression was markedly different from the 19 normal controls that we had included,” explains Dr. Kornblau. “The second thing we found was that for 24 of the 27 cytokines, there really wasn’t a difference between their expression in MDS and their expression in AML.”
Analysis of data generated in this study led to segregation of patient samples into eight different signatures. Identification of these signatures led to their correlation to different clinical leukemic features such as cytogenetics, outcome, and remission duration.
“We found to our surprise,” remarks Dr. Kornblau, “that there tended to be a good, an intermediate, and an unfavorable group of signatures. These were independent of other established clinical features like cytogenetics, like age, like having an antecedent hematological disorder. We were surprised to see that the cytokine and chemokine profiles actually were prognostic on their own.”
Dr. Kornblau explains that the results of this research set up the idea going forward that chemokine and cytokine patterns can be used to inform different therapies and enhance the ability of clinicians to affect leukemic cell growth or eliminate the resistance of those leukemic cells to different therapies already in use.
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