19/08/2020

A new technology that can detect genetic defects simultaneously in thousands of individual cells shines new light on leukemia development and how cells respond to chemotherapy. Researchers from VIB, KU Leuven and UZ Leuven, led by Prof. Jan Cools (VIB-KU Leuven Center for Cancer Biology), used a new technology to investigate the genetic defects in individual leukemia cells from patients with T-cell leukemia (T-ALL). Their results show that blood and bone marrow samples from each patient contain a variety of leukemia cells, much more than previously detected. The detection of this variety of leukemia cells gives us new information on the development of leukemia and on the response of patients to chemotherapy.

A new method

T-cell leukemia is a rare form of leukemia that most often occurs in children but can also affect adults. Just as other cancers, leukemia is caused by the accumulation of changes in the genetic material, which changes the behavior of the cells and makes them become malignant.

In previous studies, Prof. Jan Cools and Prof. Kim De Keersmaecker (KU Leuven) found that T-cell leukemia cells harbor 10 to 20 of these genetic changes, but it was impossible to tell if all the leukemia cells contained the same mutations or not. Their new research method allows to investigate more than 5000 individual cells simultaneously in each blood or bone marrow sample, obtained at diagnosis and during chemotherapy treatment of the leukemia patients.

To obtain accurate information about each individual cell, the cells are isolated from each other in small droplets that stay separate during the genetic analysis.

“This new method to analyze the genetic defects in thousands of individual leukemia cells enables us to determine differences between the leukemia cells that all look the same under the microscope,” says Prof. Jan Cools.

Tracking individual cells

The researchers investigated thousands of individual leukemia cells at diagnosis and at different time points during chemotherapy treatment. Their new data revealed that not all the leukemia cells carry the same genetic changes: there was typically a large group of leukemia cells with the same mutations accompanied by smaller subsets of cells with other mutations in each patient.

“This is important to realize,” says Prof. Cools, “as this provides new insight into how leukemia develops, and this is more complex than we anticipated.”

By analyzing leukemia cells during treatment, the researchers observed that most leukemia cells disappeared quickly (within 1-2 weeks), but that some leukemia cells with certain genetic defects were detectable for longer.

“Now that we can follow the individual leukemia cells based on the genetic defects that are present in each cell, we can get accurate information on which of these leukemia cells could be less sensitive to therapy and potentially cause disease relapse,” says Prof. Heidi Segers (UZ Leuven) who contributed to the study.

Kom op tegen Kanker provided financial support to make this research possible. Erwin Lauwers, responsible for project financing of biomedical research state at the non-profit, says: “Innovative techniques allow us to map the differences between patients so that they can receive personalized treatment. Cancer patients with a low risk of relapse can receive less intense treatment to improve their quality of life, while patients with a high risk of recurrence can be treated more efficiently to increase their odds of survival. This study could be the start of a large-scale international study to improve the prognosis and diagnosis of patients with T-cell leukemia.”

Publication

Albertí-Servera L, Demeyer S, Govaerts I, Swings T, De Bie J, Gielen O, Brociner M, Michaux L, Maertens J, Uyttebroeck A, De Keersmaecker K, Boeckx N, Segers H, Cools J. (2020). Single-cell DNA amplicon sequencing reveals clonal heterogeneity and evolution in T-cell acute lymphoblastic leukemia. Blood.

Financing

Kom op Tegen Kanker (Stand up to Cancer, the Flemish cancer society), KU Leuven, EU-funded MSCA fellowship to L. Alberti-Servera, fellowship to S. Demeyer from the Foundation against Cancer, FWO fellowships to I. Govaerts, J. De Bie, L. Alberti-Servera

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