AUTHOR=Levy Gabriel , Kicinski Michal , Van der Straeten Jona , Uyttebroeck Anne , Ferster Alina , De Moerloose Barbara , Dresse Marie-Francoise , Chantrain Christophe , Brichard Bénédicte , Bakkus Marleen 

TITLE=Immunoglobulin Heavy Chain High-Throughput Sequencing in Pediatric B-Precursor Acute Lymphoblastic Leukemia: Is the Clonality of the Disease at Diagnosis Related to Its Prognosis?

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.874771

DOI=10.3389/fped.2022.874771

ISSN=2296-2360

ABSTRACT=High throughput sequencing (HTS) of the immunoglobulin heavy chain (IgH) locus is a recent very efficient technique to monitor minimal residual disease of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). It also reveals the sequences of clonal rearrangements, hence the multiclonal structure, of BCP-ALL.
In this study, we performed IgH HTS on diagnostic bone marrow of 105 children treated between 2004 and 2008 in Belgium for BCP-ALL in the EORTC-58951 clinical trial. Patients were included irrespectively of their outcome. We described the patterns of clonal complexity at diagnosis and investigated its association with patients’ characteristics. Two indicators of clonal complexity were used: the number of foster clones, described as clones with similar D-N2-J rearrangements but other V-rearrangement and N1-joining, and the maximum across all foster clones of the number of evolved clones from one foster clone.
The maximum number of evolved clones was significantly higher in patients with t(12;21)/ETV6::RUNX1. A lower number of foster clones was associated with a higher risk group after prephase and t(12;21)/ETV6::RUNX1 genetic type.
This study observed that clonal complexity as accessed by IgH HTS, is linked to prognostic factors in childhood BCP-ALL, suggesting that it may be a useful diagnostic tool for BCP-ALL status and prognosis.