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St. Jude finds more than 100 gene variations linked with response to leukemia treatment
Date:1/27/2009

t. 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.

The study discovered 102 of the inherited genetic variations that affected the level of residual leukemia or MRD. A high proportion (21 of 102) of these MRD-linked SNPs also predicted leukemic relapse; moreover, 21 SNPs linked eradication of MRD with greater exposure of the leukemic cells to the chemotherapy drugs.

For example, the researchers discovered five SNPs that are located in and around a gene called IL15, which codes for a protein called interleukin 15 that stimulates multiplication of leukemic cells. The finding was significant because previous studies showed that IL15 protects tumors from certain chemotherapy drugs; and that it is linked to both invasion of the central nervous system by leukemic cells and an increased risk of recurrence in that area following treatment. In the current study, the team found a link between the IL15 SNPs, increased levels of IL15 in leukemia cells, and an increased risk of high MRD at the end of induction therapy.

"Our finding that IL15 plays such an important role in the failure of chemotherapy suggests that this gene may be a marker we could use to predict outcome of therapy," Relling said. "IL15 might also represent a new target for novel drugs that knock out its activity and improve the outcome of patients with high levels of this interleukin."

In addition, 21 of the 102 SNPs that predicted MRD also significantly associated with the pharmacokinetics of two antileukemic drugs, etoposide and methotrexate, which are representative of the
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Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert

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