Researchers Develop New “Stemness” Score to Predict Treatment Response in AML

Author’s Perspective

Study co-author Jean C. Y. Wang, MD, PhD: “The LSC17 score can be applied to all newly diagnosed patients with acute myeloid leukemia (AML) and is complementary to genetic [mutational] profiling. Clinicians treating AML can now obtain a rapid and accurate assessment of risk within days of diagnosis, allowing for real-time, risk-informed decision making regarding induction therapy, as well as subsequent consolidation therapy.”

High relapse rates in patients with AML have been attributed to the persistence of leukemia stem cells (LSCs), which are often resistant to standard chemotherapy and can lead to disease recurrence, even in patients who appear to go into remission. In a research letter published in Nature, investigators shared a new, rapid gene-expression test that can predict within one to two days of diagnosis whether the patient will benefit from standard chemotherapy.

Stanley W. K. Ng, MSc, from the Institute of Biomaterials and Biomedical Engineering at the University of Toronto in Ontario, Canada, and co-authors developed the LSC17 score by sampling the leukemia stem cell properties of blood or bone marrow samples from 78 AML patients, combined with molecular profiling technology that measures gene expression. They then used statistical methods to identify a set of 17 stem cell genes that were highly predictive of survival and therapy response.

The LSC signature genes included:

  • GPR56
  • AKR1C3
  • CD34
  • NGFRAP1
  • EMP1
  • SMIM24
  • SOCS2
  • CPXM1
  • CDK6
  • KIAA0125
  • DPYSL3
  • MMRN1
  • LAPTM4B
  • ARHGAP22
  • NYNRIN
  • ZBTB46
  • DNMT3B

“[The LSC17 score] provides additional prognostic/predictive information and works in all molecular subtypes of AML, with the exception of acute promyelocytic leukemia,” co-author Jean C. Y. Wang, MD, PhD, said.

Dr. Wang and researchers showed that the overall survival (OS) of patients with a high LSC17 score was significantly shorter than that of patients with a low LSC17 score (n=716 in 4 independent AML cohorts; p<0.001).

“Our study showed that patients with a high LSC17 score have a reduced chance of achieving remission and shorter overall survival following standard induction therapy, including allogeneic hematopoietic cell transplantation, compared with patients with a low score,” she explained.

This gene-signature test was adapted to the technology platform NanoString used in molecular diagnostic laboratories in Ontario. The researchers plan to conduct validation tests in a clinical laboratory setting and then in a prospective clinical trial.

The LSC17 score “provides clinicians with a rapid and powerful tool to identify AML patients who are less likely to be cured by standard therapy and who could be enrolled in trials evaluating novel upfront or post-remission strategies,” the authors wrote, noting that the study is limited in that the LSC17 score does not provide specific information about which alternative therapy would be beneficial.

Source: Ng SWK, Mitchell A, Kennedy JA, et al. A 17-gene stemness score for rapid determination of risk in acute leukaemia. Nature. 2016;540:433-7.

SHARE