Gene-sequencing leukemia research could boost Dx and treatment for kids with a rare disease subtype

St. Jude Children's Research Hospital and colleagues from around the country used next-generation sequencing in a study that could upend how a high-risk leukemia subtype is diagnosed and treated in children and adolescents.

The New England Journal of Medicine highlights their study in detail.

Researchers zeroed in on a high-risk subtype of acute lymphoblastic leukemia (ALL) known as Ph-like ALL, which occurs in some children and young adults. Their genomic analysis of 1,725 patients ages 1 to 39 who had ALL found that the rate of Ph-like ALL increases with age, and that children and young adults who get it have poor survival prospects.

As well, 91% of patients who had Ph-like ALL also had a type of chromosomal rearrangement or other genetic alterations involving activation of cytokine receptor or kinase signaling.

Further, using next-generation genetic sequencing, the researchers identified the genetic alterations that lead to Ph-like ALL, some of which were found in genes that hadn't been linked previously to cancer. They also found that gene alterations affect a small number of biological signaling pathways for the Ph-like ALL subtype. These pathways handle processes disrupted in cancer such as the regulation of genes that manage cell growth and proliferation.

The discovery helped lay the groundwork for a national trial that will begin in late 2014 or early 2015, with a focus on determining if drugs known as tyrosine kinase inhibitors (TKIs) can help improve prospects for this pediatric patient subset. Researchers hope the drug type (something not typically done now for pediatric or young adult patients with ALL) could help boost their survival prospects beyond that of chemotherapy alone. There is reason to hope, because some of the newly spotted Ph-like ALL subtypes have been found to be vulnerable to TKIs in previous studies.

While more work is needed, the diagnostic and biomarker advances in this study suggest that genetic screening could eventually enable a more personalized (and targeted) treatment for pediatric patients with this aggressive subtype of ALL once they're identified.

"The findings are tremendously exciting and pave the way for clinical trials testing TKIs plus chemotherapy in subsets of children and adolescents with ALL," corresponding author Dr. Stephen Hunger of the University of Colorado School of Medicine said in a statement.

- read the release
- get the NEJM abstract

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