Treatment of childhood leukemia has improved markedly in recent
decades, with long-term cure achieved in most patients who have access
to modern, highly intensive treatment regimens. However, some patients
develop resistance to the steroid drugs which are a key part of
combination chemotherapy treatments, which results in poor clinical
outcomes.
In the third week of PLOS Medicine's ongoing special issue on
cancer genomics, principal investigator Jules Meijerink of the Princess
Máxima Center for Pediatric Oncology, Utrecht, The Netherlands and
colleagues seek to identify mechanisms underlying treatment resistance
in children with T-cell acute lymphoblastic leukemia (T-ALL) by
combining genomic DNA sequencing and chromosomal copy-number analyses,
and suggest a new approach to therapy.
As described in their Research Article, Meijerink and colleagues studied genetic changes in leukemic cells from pediatric T-ALL patients before treatment. The researchers found specific gene mutations affecting signaling inside cells, involving the interleukin 7 receptor and downstream molecules, that were associated with steroid resistance and adverse clinical outcome. Drugs designed to target individual signaling proteins were able to restore steroid sensitivity to primary leukemic cells from patients.
Source: Eurekalert
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