DUARTE, Calif., November 15, 2011 — Patients undergoing treatment for Hodgkin or non-Hodgkin lymphoma can sometimes develop a lethal complication called therapy-related myelodysplasia (t-MDS) or acute myeloid leukemia (AML). A team of City of Hope researchers has discovered genetic markers that help identify which patients might be at risk, and are closer to understanding how physicians may prevent certain patients from developing this deadly secondary cancer. The study was published in the Nov. 15 edition of the journal Cancer Cell.

“Insights into critical molecular mechanisms contributing to susceptibility to and emergence of t-MDS/AML could provide potential targets for the development of preventive or therapeutic interventional strategies,” said Ravi Bhatia, M.D., director of the Division of Stem Cell and Leukemia Research at City of Hope, and co-principal investigator of the study.

To explore the little-known mechanisms of t-MDS/AML, lead authors Liang Li, Ph.D., staff scientist, and Sierra Min Li, Ph.D., assistant professor of the Division of Biostatistics, and a group of their fellow City of Hope researchers spent several years following a group of Hodgkin and Non-Hodgkin lymphoma patients before and after they underwent autologous hematopoietic stem cell transplantation (in which they received reinfusions of their own harvested stem cells). Some patients did well, but others developed t-MDS/AML.

Researchers compared gene expression in a training set of 18 cases that developed t-MDS/AML and 37 matched controls that did not develop t-MDS/AML. In the case of lymphoma patients who eventually developed t-MDS/AML, researchers made a startling discovery – evidence of the disease in the pre-transplant samples. “Changes associated with leukemia can actually be seen many years before the development of leukemia,” said Bhatia. “Patients and their cells and bone marrow may appear to be normal, but if you look at the deep molecular level, you can find that those changes are already there.”

The results of the training set were validated in an independent group of 36 patients (test set) consisting of 16 cases that developed t-MDS/AML after autologous transplant and 20 matched controls.

“The study has potential clinical significance, since early detection of patients at high risk for t-MDS/AML using a gene expression signature could facilitate interventions to prevent development of this lethal malignancy,” said Smita Bhatia, M.D., M.P.H., professor and Ruth Ziegler Chair in Population Sciences at City of Hope and co-principal investigator on the study.

Ravi Bhatia said the next step will be validating these findings in a larger group of patients. He also wants to explore whether patients who develop t-MDS/AML have greater risk of oxidative damage to their stem cells, and if so, whether targeting this abnormality might reduce risk of leukemia.  

This work could have broad implications, according to Smita Bhatia. Ultimately, “we may be able to apply this knowledge to healthy people who are at risk of developing cancer – especially older individuals – and modify their risk.”