Patients with acute myeloid leukemia (AML), a leukemia which arises from bone marrow tissue, often see remission following their initial treatment, but for patients whose cancer returns, there are few options. One such option is guadecitabine, a novel DNA hypomethylating drug which slows problematic changes to a person’s epigenetic profile, but the drug is ineffective in a select number of relapsed or refractory AML patients and there has not been a way to determine who stands to benefit and who does not.
However, researchers from the Coriell Institute for Medical Research have found certain biomarkers which can indicate a patient’s likelihood for success. Their findings were published in Clinical Epigenetics in July.
“Patients facing a relapse of acute myeloid leukemia face a hard road ahead of them,” said Woonbok Chung, PhD, a principal research scientist at Coriell and the paper’s first author. “Hypomethylating agents such as guadecitabine have potential to extend lives, but it’s critical that we know who is most likely to benefit and who is not. This reduces wasted time and resources at a time when both are especially precious.”
Led by Jean-Pierre Issa, MD, Chief Executive Officer and President of Coriell and the paper’s senior author, the team of researchers studied about 130 patients enrolled in phase 1 and 2 trials, measuring their genome-wide DNA methylation, 54 gene mutations and the gene expression of seven genes prior to treatment with the drug. These patients were then given guadecitabine at therapeutic doses and their outcomes were tracked.
The researchers found a subset of patients – about 20 percent of the cohort – did not respond to the drug. This group was identified by a unique gene expression pattern, RAS mutations, high levels of CpG island methylation, and high bone marrow (BM) and peripheral blood (PB) blast cells.
Researchers also identified that a high hemoglobin level and low PB blast counts were the best predictors of complete remission. Other factors, such as certain gene expression signatures, cytogenetics, hemoglobin, and RAS mutations could be used to predict overall survival.
Coriell’s Jaroslav Jelinek, MD, PhD, Chief Research Officer, was also a co-author on the study.
This study was supported by the National Institutes of Health (grants R01CA158112 and P50CA100632) and by a grant from Astex Pharmaceuticals, the maker of guadecitabine.
