Journal Article

The evolution of relapse of adult T cell acute lymphoblastic leukemia

García-Hernández, Violeta, Gonzalez, Celia, Espinosa, Lluís, Sentís, Inés, Gonzalez, Jessica, Mularoni, Loris, Ribera, Josep-Maria, López-Arribillaga, Erika, Bellosillo, Beatriz, Gonzalez-Perez, Abel, Gonzalez, Santiago, Genescà, Eulalia, Bigas, Anna, Lopez-Bigas, Nuria, Fernandez-Ibarrondo, Lierni, Muiños, Ferran

2020

Overview

Background Adult T cell acute lymphoblastic leukemia (T-ALL) is a rare disease that affects less than 10 individuals in one million. It has been less studied than its cognate pediatric malignancy, which is more prevalent. A higher percentage of the adult patients relapse, compared to children. It is thus essential to study the mechanisms of relapse of adult T-ALL cases. Results We profile whole-genome somatic mutations of 19 primary T-ALLs from adult patients and the corresponding relapse malignancies and analyze their evolution upon treatment in comparison with 238 pediatric and young adult ALL cases. We compare the mutational processes and driver mutations active in primary and relapse adult T-ALLs with those of pediatric patients. A precise estimation of clock-like mutations in leukemic cells shows that the emergence of the relapse clone occurs several months before the diagnosis of the primary T-ALL. Specifically, through the doubling time of the leukemic population, we find that in at least 14 out of the 19 patients, the population of relapse leukemia present at the moment of diagnosis comprises more than one but fewer than 10 8 blasts. Using simulations, we show that in all patients the relapse appears to be driven by genetic mutations. Conclusions The early appearance of a population of leukemic cells with genetic mechanisms of resistance across adult T-ALL cases constitutes a challenge for treatment. Improving early detection of the malignancy is thus key to prevent its relapse.

• Publisher: BioMed Central,Springer Nature B.V
• Subject: Acute lymphoblastic leukemia / Adults / Animal Genetics and Genomics / Bioinformatics / Biomedical and Life Sciences / Cancer Evolution and Metastasis / Diagnosis / evolution / Evolutionary Biology / genome / Genomes / Genomics / Human Genetics / Leukemia / Life Sciences / Lymphatic leukemia / Lymphocytes T / lymphocytic leukemia / Malignancy / Microbial Genetics and Genomics / Mutation / Patients / Pediatrics / Plant Genetics and Genomics / Rare diseases / relapse / T-lymphocytes / Tumors / young adults