Nav: Home

Inherited genetic variant influences response to leukemia treatment for some children

September 11, 2020

Scientists at St. Jude Children's Research Hospital are investigating the inherited genetics of childhood leukemia and how particular gene variations can affect treatment outcomes. The research showed that an inherited variation in the GATA3 gene strongly influences early response to chemotherapy and is linked to relapse in children with acute lymphoblastic leukemia (ALL). The work was published as an advance online publication this week in the Journal of the National Cancer Institute.

Minimal residual disease (MRD) checks for the presence of minute numbers of cancer cells after induction therapy, the first stage of ALL treatment. MRD is one of the strongest predictors of relapse risk for young ALL patients.

"We know there is substantial variability in the way patients respond to ALL therapy. Certain mutations in leukemia cells are associated with drug response, but they certainly do not explain the full spectrum of the observed variability. This is when we realize we need to look at inherited genetic variants as well," said corresponding author Jun J. Yang, Ph.D., of St. Jude Pharmaceutical Sciences and Oncology.

The team conducted a genome-wide association study on children in Children's Oncology Group clinical trials for high-risk B-ALL. This cohort was large enough for the scientists to look for associations between the inherited genetics and end-of-induction MRD levels for 863,370 single nucleotide polymorphisms.

Results of the study showed that an inherited GATA3 variant strongly influenced how patients responded to therapy. This variant is also associated with relapse. GATA3 is known by scientists to encode a crucial transcription factor for the development and differentiation of T cells.

"This variant isn't completely new to us; we've previously found it to be associated with susceptibility to Philadelphia chromosome-like ALL, a rare but high-risk subtype," Yang said. "These new findings about the relationship between the GATA3 variant and MRD solidify the potential utility of inherited variants in how we assess newly diagnosed patients for risk-stratified therapy."
-end-
First author of the study is Hui Zhang, M.D., Ph.D., formerly of St. Jude and now of Guangzhou Women and Children's Medical Center. The study's other St. Jude authors include Mary Relling, Ching-Hon Pui, Charles Mullighan, William Evans, Anthony Pak-Yin Liu, Seth Karol, Wenjian Yang, Deqing Pei and Cheng Cheng. Other authors are Meenakshi Devidas and Yunfeng Dai of the University of Florida, Gainesville; Shawn HR Lee of Khoo Teck Puat-National University Children's Medical Institute, Singapore; Xueyuan Cao of University of Tennessee Health Science Center; Michael Borowitz of Johns Hopkins Medical Institute; Brent Wood of the University of Washington, Seattle; Julie M. Gastier-Foster of Nationwide Children's Hospital; Elizabeth Raetz and William Carroll of Stephen D. Hassenfeld Children's Center for Cancer & Blood Disorders; Eric Larsen of Maine Children's Cancer Program; Naomi Winick of University of Texas Southwestern Medical Center; W. Paul Bowman of Cook Children's Medical Center; Paul Martin of Duke University; Stephen Hunger of Children's Hospital of Philadelphia and University of Pennsylvania; and Mignon Loh of Benioff Children's Hospital and University of California, San Francisco.

The research was funded in part by grants from the National Institutes of Health (CA21765, CA98543, CA114766, CA98413, CA180886, CA180899, GM92666, GM115279 and GM097119); a St. Baldrick's Foundation International Scholar award; a National Medical Research Council Singapore Research Training Fellowship; and ALSAC, the fundraising and awareness organization of St. Jude.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food -- because all a family should worry about is helping their child live. To learn more, visit stjude.org or follow St. Jude on social media at @stjuderesearch.

St. Jude Children's Research Hospital

Related Acute Lymphoblastic Leukemia Articles:

Call for caution for using a CAR-T immunotherapy against acute myeloid leukemia
Researchers from the Josep Carreras Leukaemia Research Institute prove that the preclinical implementation of Acute Myeloid Leukaemia immunotherapy, based on CD123-redirected CAR T-cells, affects hematopoiesis, blood cells production, and reconstitution.
For acute myeloid leukemia, genetic testing is often worth the wait
New tailored therapies offer exciting prospects for treating acute myeloid leukemia (AML), but taking advantage of them may require waiting a week or more for genetic testing before starting treatment, posing a dilemma for doctors and patients facing this deadly and often fast-moving disease.
Discovery in human acute myeloid leukemia could provide novel pathway to new treatments
Researchers at Mount Sinai have discovered that human acute myeloid leukemia (AML) stem cells are dependent on a transcription factor known as RUNX1, potentially providing a new therapeutic target to achieve lasting remissions or even cures for a disease in which medical advances have been limited.
Oncotarget Acute promyelocytic leukemia (APL): a review of the literature
Oncotarget Volume 11, Issue 11 reported that relapsed APL, particularly in the high-risk subset of patients, remains an important clinical problem.
Study reveals properties of cells fated to relapse in acute lymphoblastic leukemia
Researchers have found that genetically defined subpopulations of leukemia cells present at diagnosis have distinct characteristics that lead to relapse.
Research revises classification of acute myeloid leukemia & myelodysplastic syndrome
Findings presented as a late-breaking abstract at the American Society of Hematology annual meeting by St.
Researchers discover therapy to treat drug-resistant acute lymphoblastic leukemia
Researchers from Case Western Reserve University School of Medicine have developed a new combination treatment regimen that enhances the immune system's ability to kill leukemias that do not respond to standard treatments.
New drug providing hope for babies with aggressive Acute Lymphoblastic Leukaemia
A breakthrough new drug is providing hope to tiny babies at risk of dying from an aggressive form of Acute Lymphoblastic Leukaemia and could help all cancer patients.
Recovery twice as hard for survivors of childhood acute lymphoblastic leukemia
The cardiorespiratory fitness of survivors of childhood acute lymphoblastic leukemia is 22% worse than that general Canadian population,and genetics might play a role, an UdeM researcher finds.
First major study of proteins in patients with acute lymphoblastic leukaemia
The most common form of childhood cancer is acute lymphoblastic leukaemia (ALL).
More Acute Lymphoblastic Leukemia News and Acute Lymphoblastic Leukemia Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.