Finding New Treatment Options for Leukemias

Researchers identified mutations in leukemias that may make them amenable to FDA-approved ALK inhibitors

Using genomic sequencing, researchers identified two mutations in the anaplastic lymphoma receptor tyrosine kinase (ALK) gene of two patients’ leukemias. Laboratory studies showed that leukemias that have these mutations may respond to U.S. Food and Drug Administration (FDA)-approved ALK inhibitors such as crizotinib and ceritinib.

The study was recently published in Cancer Research, a journal of the American Association for Cancer Research.

“Genetic lesions involving ALK have been seen recurrently in a number of different types of solid tumors, but to my knowledge, ALK mutations have not previously been implicated as a major contributor to leukemia,” said Jeffrey Tyner, PhD, an assistant professor in the Department of Cell, Developmental, and Cancer Biology at the Knight Cancer Institute at Oregon Health & Science University and the senior author of the study. “The discovery of new mutant versions of ALK that may contribute to the development of leukemia and can be therapeutically targeted suggests new treatment options for patients with leukemia with ALK mutations.”

Using a technology called deep sequencing, Tyner and colleagues analyzed 185 tumor samples, including samples of acute lymphoblastic leukemia (AML), acute myeloid leukemia (ALL), and myeloproliferative neoplasms. Of these, two samples – one from a pediatric patient with B-cell ALL and one from an adult patient with AML – had one mutation each, in the ALK gene.

An estimated 6,250 and 20,830 people in the United States will be diagnosed with ALL and AML, respectively, and about 1,450 and 10,460 will die from these two diseases, respectively, in 2015, according to the National Cancer Institute report.

The researchers conducted further studies in the laboratory and found that the ALK mutations had the potential to make a cell cancerous and drive abnormal cell growth. They also learned that leukemia cells harboring either of the two mutations could be inhibited by several ALK inhibitors, including crizotinib and ceritinib, two therapeutics approved by the FDA for the treatment of ALK-positive metastatic non-small cell lung cancer.

“These findings suggest that broader use of ALK inhibitors should be considered and that these drugs could be applied on the basis of genetic features of a patient’s tumor cells,” said the study’s lead author, Julia Maxson, PhD, who is presently a postdoctoral fellow in the Clinical Research Division at Fred Hutchinson Cancer Research Center in Seattle.