Childhood B cell leukemia: Intercepting the paths to progression.

B-cell Acute Lymphoblastic Leukemia (B-ALL) is the most common pediatric cancer, arising most often in children aged 2-5 years. This distinctive age distribution hints at an association between B-ALL development and disrupted immune system function during a susceptible period during childhood, possibly triggered by early exposure to infection. While cure rates for childhood B-ALL surpass 90% in high-income nations, survivors suffer from diminished quality of life due to the side effects of treatment. Consequently, understanding the origins and evolution of B-ALL, and how to prevent this prevalent childhood cancer, is paramount to alleviate this substantial health burden. This article provides an overview of our current understanding of the etiology of childhood B-ALL and explores how this knowledge can inform preventive strategies.

Childhood B-Cell Preleukemia Mouse Modeling.

Leukemia is the most usual childhood cancer, and B-cell acute lymphoblastic leukemia (B-ALL) is its most common presentation. It has been proposed that pediatric leukemogenesis occurs through a "multi-step" or "multi-hit" mechanism that includes both in utero and postnatal steps. Many childhood leukemia-initiating events, such as chromosomal translocations, originate in utero, and studies so far suggest that these "first-hits" occur at a far higher frequency than the incidence of childhood leukemia itself. The reason why only a small percentage of the children born with such preleukemic "hits" will develop full-blown leukemia is still a mystery. In order to better understand childhood leukemia, mouse modeling is essential, but only if the multistage process of leukemia can be recapitulated in the model. Therefore, mouse models naturally reproducing the "multi-step" process of childhood B-ALL will be essential to identify environmental or other factors that are directly linked to increased risk of disease.

Genomic Inverse PCR for Screening of Preleukemic Cells in Newborns (GIPFEL Technology).

Recurrent chromosomal translocations define genetic subtypes of childhood leukemia and present the first hit that generates an expanded clone of preleukemic cells in the bone marrow. Most commonly, reverse transcriptase PCR is used to detect these translocations on RNA level. This technique has severe drawbacks, including sensitivity to contamination and instability of RNA. Here, we describe the genomic inverse PCR for exploration of ligated breakpoints (GIPFEL) that overcomes these pitfalls.