This is part of a periodic series of Q&A’s with LLS-funded researchers. Dr. Abdel-Wahab of Memorial Sloan Kettering Cancer Center focuses on an area of research called epigenetics – chemical modifications that regulate (switch on and off) gene activity. He is studying how these processes drive the development of acute myeloid leukemia and other blood cancers. He currently holds a Career Development Program grant from LLS, a program that supports scientists earlier in their careers.
Q. What is the focus of your research and its primary goal?
My research is focused on understanding the genetic changes in leukemias and lymphomas in hopes of developing new selective treatments for patients targeting these cancerous changes. We have contributed to studies in acute myeloid leukemia, myelodysplastic syndromes, chronic lymphocytic leukemia, hairy leukemia, and histiocytic neoplasms. Among our findings is that there is frequently an overlap of two mutations in AML patients, of the SRSF2 and IDH2 genes. This could open the door to more targeted approaches to treating patients who have both of these mutations.
Q. How will blood cancer patients benefit from your work?
We hope that our studies will result in the discovery of new therapeutic approaches for blood cancer patients as well as new biomarkers for the treatment of blood cancers. To date, our work has helped result in the FDA approval of drugs for histiocytosis patients and several drugs in early phase clinical trials for patients with the myelodysplastic syndromes and acute myeloid leukemia.
Q. Why were you drawn to blood cancer research?
I have always been fascinated by the blood system and the immune system. Blood cancers develop due to alterations in the normal development of blood and immune cells and hence the study of blood cancers was a natural fit for my interests. I am also highly motivated by the fact that there is still a great need for better treatments for patients with many forms of blood cancer such as acute myeloid leukemia and the myelodysplastic syndromes, in particular.
Q. How has LLS helped advance your research career?
LLS has supported me in every stage of my career- from my time as a trainee to my current position as a mid-career faculty member. In addition, LLS has supported multiple trainees in many labs, several of whom have gone on to start their own research labs at universities and hospitals in the U.S., France, Japan, and South Korea.
Q. What makes you want to get out of bed in the morning?
I am motivated by the need to develop more effective and safer therapies for patients with blood cancers. I am so excited by the prospect that there are many mysteries underlying the development of blood cancers which have yet to be uncovered-- many of which could result in amazing new treatments for patients.
All 9/11 responders put their own lives at risk to save others from the events that occurred at the World Trade Center (WTC) on September 11, 2001, in New York City. Since then, several studies have shown elevated rates of cancers such as multiple myeloma, prostate cancer and thyroid cancer among first responders and those who worked nearby.
Today, a new study published in the journal JNCI Cancer Spectrum adds another cancer to that list, leukemia, which is a cancer of the blood and bone marrow. Researchers of this study examined cancer incidence in nearly 29,000 first responders, including law enforcement, construction, and telecommunications workers who had some level of exposure to the WTC dust.
While the study did not find a clear relationship between length of time or the intensity of exposure in the development of cancer, researchers did identify several risk factors that were linked to a higher risk of developing cancer including age, gender and smoking status.
Some may question why the findings of increased risk of leukemia, specifically, have just come to the forefront now, nearly two decades after 9/11. The study’s author, Susan Teitelbaum, PhD, professor of environmental medicine and public health at the Icahn School of Medicine at Mount Sinai in New York City, said, “Previously the sample size wasn't large enough to detect an association.”
In an interview with Medscape Dr. Gwen Nichols, Chief Medical Officer at The Leukemia & Lymphoma Society, explains, “Associations of older age and smoking are not surprising. Leukemia can take years to develop after exposure to a carcinogen, so past studies may have been completed too early to pick up on a heightened risk. Many earlier studies were also smaller, and since leukemia is relatively rare, these samples may not have included enough patients to conduct a full analysis.”
Dr. Nichols elaborates, “It is also highly unlikely that any one exposure is unifactorial when it comes to leukemia. If someone is at higher risk, such as a smoker or being older, then exposure to environmental toxins may increase the risk more, as opposed to someone without those factors," she said. "What we know about causes of leukemia — from the standpoint of exposure to toxins — is limited. It would be great to learn more, especially in this era of genetic testing, and be able to tell people how to help reduce their risks."
According to Dr. Nichols, ongoing research may shed some light on a "genetic link" between exposure and the development of leukemia. Healthy individuals who are not diagnosed with a blood cancer, but are found to have a group of cells with an acquired gene mutation known as clonal hematopoiesis of indeterminate potential, have been found to be more prone to developing leukemia as they age.
"The Leukemia & Lymphoma Society is currently supporting research that is looking at the development of CHIP over time, for multiple myeloma and leukemia," said Nichols. "This study looked at the development of CHIP in first responders, and they saw an increase in clonal CHIP that was higher than what one would expect, as compared to age matched controls."
The findings reported in this study suggest exposure could be causing increases in mutational changes. "It has a fairly long latency and that may partially explain why we're seeing more leukemia now,” said Dr. Nichols.
The study is ongoing, and Dr. Nichols said she is "hopeful that a paper will published when the research is completed."
LLS also provides resources and information on the risks to fire fighters. Learn more here.
NCI Cancer Spectr. Published January 14, 2020. Full text