The kinetics of blast clearance are associated with copy number alterations in childhood B-cell acute lymphoblastic leukemia.

Autor: Urbańska Z; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Lejman M; Laboratory of Genetic Diagnostics, Medical University of Lublin, Lublin, Poland., Taha J; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Madzio J; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Ostrowska K; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Miarka-Walczyk K; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Wypyszczak K; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Styka B; Laboratory of Genetic Diagnostics, Medical University of Lublin, Lublin, Poland., Jakubowska J; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Sędek Ł; Department of Pediatric Hematology and Oncology, Medical University of Silesia, Zabrze, Poland., Szczepański T; Department of Pediatric Hematology and Oncology, Medical University of Silesia, Zabrze, Poland., Stańczak M; Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland., Fendler W; Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland; Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Młynarski W; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Pastorczak A; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland. Electronic address: agata.pastorczak@umed.lodz.pl.
Jazyk: angličtina
Zdroj: Neoplasia (New York, N.Y.) [Neoplasia] 2023 Jan; Vol. 35, pp. 100840. Date of Electronic Publication: 2022 Oct 23.
DOI: 10.1016/j.neo.2022.100840
Abstrakt: We analyzed the pattern of whole-genome copy number alterations (CNAs) and their association with the kinetics of blast clearance during the induction treatment among 195 pediatric patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) who displayed intermediate or high levels of minimal residual disease (MRD). Using unsupervised hierarchical clustering of CNAs > 5 Mbp, we dissected three clusters of leukemic samples with distinct kinetics of blast clearance [A - early slow responders (n=105), B - patients with persistent leukemia (n=24), C - fast responders with the low but detectable disease at the end of induction (n=66)] that corresponded with the patients' clinical features, the microdeletion profile,the presence of gene fusions and patients survival. Low incidence of large CNAs and chromosomal numerical aberrations occurred in cluster A which included ALL samples showing recurrent microdeletions within the genes encoding transcription factors (i.e., IKZF1, PAX5, ETV6, and ERG), DNA repair genes (XRCC3 and TOX), or harboring chromothriptic pattern of CNAs. Low hyperdiploid karyotype with trisomy 8 or hypodiploidy was predominantly observed in cluster B. Whereas cluster C included almost exclusively high-hyperdiploid ALL samples with concomitant mutations in RAS pathway genes. The pattern of CNAs influences the kinetics of leukemic cell clearance and selected aberrations affecting DNA repair genes may contribute to BCP-ALL chemoresistance.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
(Copyright © 2022. Published by Elsevier Inc.)
Databáze: MEDLINE