The findings are important because although cure rates for ALL exceed 80 percent, patient responses vary significantly to the same drugs. Much of this variance has been unexplained. The newly discovered genetic variations, however, will likely give scientists a clearer understanding of why treatments fail in some patients with ALL, and how to predict early in treatment which children could be successfully treated with less aggressive treatment.
"This study differs from most previous investigations of gene variations linked to
In their research, St. Jude scientists collaborated with a team from COG, a worldwide group of medical institutions that cooperate in laboratory research studies and clinical trials of cancer treatments for children. Instead of studying genetic variations acquired by
The researchers then determined which of those small, inherited variations, called single-nucleotide polymorphisms (SNPs), were associated with minimal residual disease (MRD). MRD is the small number of leukemic cells that survive after remission induction therapy—the initial treatment. This measurement helps clinicians identify patients whose disease is highly responsive to chemotherapy and therefore might be cured with milder and less-toxic treatment; and also shows if remission induction therapy will likely fail.
The researchers performed a search of 476,796 inherited SNPs from two independent groups of children with newly diagnosed ALL: 318 patients on clinical trials at St. Jude and 169 patients on COG clinical trials.
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