Study identifies chromosomal aberrations associated with childhood B-ALL relapse frequent subtype

An international research team, coordinated by Dr. Oscar Molina and Dr. Pablo Menéndez, of the Josep Carreras Leukemia Research Institute, identifies chromosomal aberrations associated with relapse in a frequent subset of B cell Acute lymphoblastic leukemia (B-ALL), a serious condition that mainly affects children. This finding may help identify those patients at higher risk of relapse at diagnosis to guide them toward more appropriate treatment options and anticipate cancer recurrence.

The research, published in the specialist journal Molecular Oncology, confirmed that hyperdiploid B-ALL, a common subtype of B-ALL in children, is associated with high genetic heterogeneity with variable chromosome numbers in leukemic cells. The results showed that chromosome 10 and 18 trisomies are good prognosis markers that can be used to predict relapse risk and to decide the most appropriate treatment strategies for these patients.

In addition, the study also found that clonal genetic variability is responsible for the appearance of specific chromosomal combinations that become predominant and thus showed that lower clonal heterogeneity can be used as another marker to predict relapse risk in hyperdiploid B-ALL patients.

According to the lead authors, Mireia Ramos from the Autonomous University of Barcelona and Juan L. Trincado, from the Josep Carreras Institute, classical karyotyping lacks the observed high genetic variability and other techniques such as iFISH and single cell sequencing would be advised to facilitate the initial cytogenetic diagnosis in the high-hyperdiploid B-ALL entity in children.

B-ALL is the most common childhood blood malignancy, with nearly 3 out of 4 cases occurring in children under the age of 6. It is characterized by the accumulation of B cell precursors in the bone marrow, leading to underproduction of mature B cells, an essential part of our immune system, and other types of blood cells. A common feature of this type of cancer is the presence of aberrant gains or losses of whole chromosomes in the leukemic cells.

When the gain is too high, such as more than 5 extra chromosomes, clinicians consider it hyperdiploidy (diploidy refers to the usual set of chromosomes, which occur in pairs in most human cells), a good prognosis marker, and patients with these characteristics usually show a complete response after treatment.

However, relapses of cells escaping treatment are not uncommon, meaning that some of the chromosome instability seen in hyperdiploid B-ALL may benefit the malignant cells in some way. To find out how, researchers wanted to know whether specific chromosomal gains were linked to the emergence of resistant clones and a greater chance of relapse.

They analyzed cells from 72 Hyperdiploidy B-ALL patients, 62 from initial diagnosis and 10 after relapse. The computational analysis of single-cell genetic data from those samples allowed the researchers to identify new prognostic markers to improve patients’ relapse risk assessment using techniques commonly used by clinical hematoncology labs. The results showed that, while extra 10 and 18 chromosomes were associated with a good prognosis, low clonal heterogeneity – due to clonal selection of the “fitter” clones – meant a higher risk of relapse and lower survival rates.

Overall, this new research provides a new perspective on high hyperdiploid B-ALL and proposes new tools to help clinicians better understand their patients’ future outcomes and improve individual survival.


Reference magazine:

Ramos-Muntada, M., et al. (2022) Clonal heterogeneity and percentages of specific chromosome gains are risk predictors in childhood high hyperdiploid B-cell acute lymphoblastic leukemia. Molecular Oncology.

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