An international team of researchers have developed new tools to predict relapse risk in high hyperdiploid B-cell acute lymphoblastic leukaemia (HHD-B-ALL).
A team coordinated by Dr Oscar Molina and Dr Pablo Menéndez, from the Josep Carreras Leukaemia Research Institute, Spain, identified chromosomal abnormalities linked to relapse in HHD-B-ALL, a frequent subtype which particularly affects children.
They confirmed that HHD-B-ALL is associated with a high genetic heterogeneity with variable chromosome numbers in leukaemic cells.
The researchers set out to identify patients at diagnosis who are at a higher risk of relapse so they can be directed to more appropriate treatment options.
The presence of chromosome 10 and 18 trisomies (three copies of the chromosome rather than two) were found to be good prognostic markers for relapse risk; lower rates of 10 and 18 trisomy among leukaemia cells predicted higher risk of relapse.
They also found clonal genetic variability is responsible for the appearance of specific chromosomal combinations that dominate over time. The team went on to demonstrate that lower clonal heterogeneity is associated with higher relapse risk in HHD-B-ALL patients.
Lead authors Mireia Ramos and Juan L. Trincado, of the the Autonomous University of Barcelona and the Josep Carreras Institute respectively, said classical karyotyping misses the high genetic variability observed. Other techniques, such as iFISH and single cell sequencing, refine the initial cytogenetic diagnosis in the childhood high-hyperdiploid B-ALL entity, they say.
The study team analysed 72 samples from HHD-B-ALL patients, 62 of which were from first diagnosis and 10 matched relapse samples.
By completing computational analysis of single-cell genetic data, they identified new prognostic markers to improve the relapse risk assessment of patients.
The findings, published in Molecular Oncology, propose new tools so clinicians can better understand their patients’ possible outcomes and improve the survival rates.
Source:
Ramos-Muntada M, Trincado JL, Blanco J, Bueno C, Rodríguez-Cortez VC, Bataller A, López-Millán B, Schwab C, Ortega M, Velasco P, Blanco ML, Nomdedeu J, Ramírez-Orellana M, Minguela A, Fuster JL, Cuatrecasas E, Camós M, Ballerini P, Escherich G, Boer J, denBoer M, Hernández-Rivas JM, Calasanz MJ, Cazzaniga G, Harrison CJ, Menéndez P, Molina O. (2022) “Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukaemia.” Molecular Oncology, doi: 10.1002/1878-0261.13276.
Link: https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13276
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