B-cell acute lymphoblastic leukaemia is the most common form of childhood cancer. In this type of cancer, which affects blood cells, one of the most common abnormalities is the presence of cells with an excess of chromosomes (hyperdiploidy), a condition that leads to chromosomal instability. Now, a study published in Cell Reports reveals that this chromosomal instability caused by hyperdiploidy reduces the proliferation of the affected cells, delays their differentiation and allows some to persist as rare, long-lived clones in the bone marrow, but without triggering leukaemia.
The study, conducted using animal models, is led by professors and researchers Òscar Molina and Pablo Menéndez from the Faculty of Medicine and Health Sciences of the University of Barcelona and the Josep Carreras Leukaemia Research Institute. The paper, whose lead author is Namitha Thampi, also a member of both institutions, is supported by the Spanish Association Against Cancer (AECC).
The study proposes a two-stage model to explain the origin of childhood B-cell acute lymphoblastic leukaemia (B-ALL): an initial prenatal stage - hyperdiploidy - and a subsequent postnatal stage - triggered by unknown factors - which is necessary to initiate the malignant transformation of rare clones and lead to the development of the disease.
From the first phase (hyperdiploidy) to the second (malignant transformation), there may be a time window of between two and six years, which corresponds to the peak incidence of childhood lymphoblastic leukaemia. It remains unclear how these rare clones evolve to cause the disease, and understanding this will be key to designing future strategies for the prevention of childhood leukaemia.
Cells with more chromosomes than necessary
This type of lymphoblastic leukaemia can develop when a child's immune system responds excessively to a common infection. This response involves the production of large amounts of cytokines and proliferation signals that stimulate the bone marrow cells to divide and produce new immune cells.
"If the pre-leukaemic clone with extra chromosomes is present among these cells, it also receives growth signals and can proliferate more than normal. Increased cell division raises the likelihood of further genetic errors. If the clone acquires synergistic mutations, it may eventually develop into leukaemia," says Òscar Molina, a member of the UB's Department of Physiological Sciences.
