Researchers pinpoint genetic cause of disease

A rare but often-deadly form of childhood leukemia can be triggered by the fusion of two genes that normally remain separate, according to a new study involving scientists at St. Jude Children’s Research Hospital.

Nearly 30 percent of the cases of acute megakaryoblastic leukemia were traceable to a genetic misstep on chromosome 16, one of the 23 pairs of chromosomes present in nearly all human cells, according to a paper by researchers at St. Jude and Washington University in St. Louis. In the process, the chromosome becomes rearranged, bringing together pieces of two genes and resulting in the production of an abnormal protein.

The protein, in turn, switches on genes that tell immature blood cells to proliferate uncontrollably, leading to leukemia.

The finding, published this week in the journal Cancer Cell, was the latest of several derived from the Pediatric Cancer Genome Project, a three-year, $65 million effort by St. Jude and Washington to decode the genetic alterations that lead to cancer.

The discovery of the genetic alteration should help in the development of new therapies to treat the disease, said Dr. Tanja Gruber, assistant member in St. Jude’s department of oncology, who was lead author of the study.

“Once we understand the disorder it causes in the cell, we can actually find drugs that ... interfere with that process,” Gruber said.

“Otherwise, we’re just taking stabs in the dark.”

Dr. James Downing, scientific director at St. Jude and corresponding author of the paper, said in addition to helping develop new therapies, the new findings will let doctors know that patients with the fused genes won’t respond well to traditional treatment. “You need to try something different,” he said.

AMKL is a subtype of acute myeloid leukemia, the disease afflicting about 40 new patients to St. Jude each year.

About 10 percent of acute myeloid leukemia patients have AMKL.

Some types of patients with AMKL have a good prognosis. But for the nearly 30 percent of them who contract the disease because of the protein created by the fused genes, the outlook is grim. Studies showed only 34.3 percent of them were alive five years after diagnosis.

“It is a very rare disease, but it is a disease that has a very poor outcome, so that is why we focused on it,” Downing said.