A technique reveals how the same mutations cause very different leukemias

Myeloid leukemias are among the most aggressive blood cancers and have low survival rates. Today, patients with leukemia undergo genetic testing to determine which mutations they have and to choose the best treatment. However, even among patients with the same mutation, the progression of the disease and the response to therapy can be very different.

A study by IRB Barcelona , ​​funded by the CRIS Foundation against cancer and led by ICREA researcher 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 that is "stronger" and the other more "sensitive" to inflammatory stimuli. This prior characteristic influences the way in which the disease evolves after acquiring mutations in the oncogenes.

"By incorporating mutations, both cellular states can lead to leukemia, but with different biological properties that respond differently to therapy," explains Rodríguez-Fraticelli.

The discovery, published in the journal ' Cell Stem Cell ', represents a step forward in understanding the great variety that exists in this type of cancer and underlines the importance of analysing the cellular "state" prior to the mutation.

To carry out this research, the team developed the STRACK (Simultaneous Tracking of Recombinase Activation and Clonal Kinetics) technique. STRACK uses genetic barcodes to track each cell and record its behavior before and after the mutation.

"This strategy has made it possible, for the first time, to link the initial state of each cell with its subsequent cancerous characteristics," explain Indranil Singh and Daniel Fernández Pérez, first authors of the study.

Furthermore, the use of mouse models has allowed us to study this process in a complete physiological environment, and with controlled genetic characteristics, which reinforces the relevance of the findings.

The findings of this study suggest that, at least in the case of leukemia, it is not enough to identify the genetic mutation to decide on the best treatment . The "previous state" of the cells, which may include their reaction to repeated inflammation or epigenetic changes, is decisive when predicting the type of tumor and its reaction to drugs.

This could extend to other cancers, since cells in different tissues also accumulate "memories" of inflammation or other damage, which would affect their behavior. Knowing these factors, in addition to the 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.