Myeloid leukemia are within the most aggressive blood cancers and have low survival rates. Today, patients with leukemia are performed a genetic analysis to know what mutations they have and thus choose the best treatment. However, even among patients presenting the same mutation, the progression of the disease and the response to therapy can be very different.
A study of IRB Barcelonafinanced by the CRISOR FOUNDATION And led by the researcher Icrea, Alejo Rodríguez-Fraticelli, has now revealed that these differences can be explained because not all blood stem cells respond in the same way when they acquire a mutation, and the previous “state” of the cell influences The development of cancer.
Specifically, scientists have identified two cell types, one more “strong” and others more “sensitive” to inflammatory stimuli. This previous characteristic influences the way the disease evolves after acquiring mutations in oncogenes.
“By incorporating mutations, both cell states can lead to leukemia, but with different biological properties that respond differently to therapy,” explains Rodríguez-Fraticelli.
The finding, published in the magazine ‘Cell Stem Cell‘, is a step forward in the understanding of the great variety that exists in this type of cancers and underlines the importance of analyzing the cellular “state” prior to the mutation.
In order to carry out this research, the team developed the Strack technique (of English Simultaneous Tracking of Recombine Activation and Clonal Kinetics). Strack uses genetic barcodes to track each cell and record their behavior before and after the mutation.
“This strategy has allowed, for the first time, to link the initial state of each cell with its posterior cancer characteristics,” explain Indranil Singh and Daniel Fernández Pérez, first study authors.
Predict the tumor
In addition, the use of mouse study models has allowed studying this process in a complete physiological environment, and with controlled genetic characteristics, which reinforces the relevance of the findings.
The conclusions of this work that suggest that, at least in the case of leukemia is not enough to identify the genetic mutation to decide the best treatment. The “previous state” of the cells, which may include its reaction against repeated inflammations or epigenetic changes, is decisive when predicting the type of tumor and its reaction to drugs.
This could be extended to other cancers, since cells in different tissues also accumulate “memories” of inflammation or other damages, which would affect their behavior. Knowing these factors, in addition to mutation, would help develop even more personalized treatments and preventive strategies that focus on avoiding habits that predispose to the development of the most aggressive variants of the disease.
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