Precision care for a high-risk type of leukemia
Testing for minimal residual disease (MRD) can help some patients avoid bone marrow transplantation. MRD occurs when a low level of cancer cells remain after a patient has finished the initial therapy for cancer.
MRD can be used to guide care. It helps clinicians know when to intensify or reduce treatment.
Many physicians still use transplantation to treat hypodiploid acute lymphoblastic leukemia (ALL). This disease is rare and generally has poor outcomes.
St. Jude scientists compared treatment outcomes between hypodiploid patients treated with transplantation or chemotherapy based on their level of MRD. The study found that for patients treated with MRD-guided therapy, transplantation did not significantly improve patients’ survival. This was especially true for patients with no MRD after therapy to induce remission.
“This study confirms our earlier observation that patients with hypodiploid ALL who have no evidence of MRD should not be transplanted,” said Ching-Hon Pui, MD, St. Jude Oncology chair.
The findings appeared in the Journal of Clinical Oncology.
Refining how leukemia is classified
St. Jude researchers are like explorers filling in a map. They identified new subtypes of the most common childhood cancer, B-cell acute lymphoblastic leukemia (B-ALL).
The research will provide more information about the biology of B-ALL. This is likely to improve the diagnosis and treatment of high-risk disease.
Using genomic tools, the researchers studied nearly 2,000 children and adults with B-ALL. The findings show that B-ALL has 23 subtypes.
The St. Jude team identified eight new subtypes in this study. These subtypes have distinct genomic and clinical features and outcomes. Through this work, two-thirds of the previously uncharacterized B-ALL patients can be classified into subtypes.
“B-ALL has remarkable molecular diversity,” said Charles Mullighan, MBBS, MD, of St. Jude Pathology. “This diversity helps drive precision medicine to improve B-ALL treatment and outcomes.”
The research appeared in the journal Nature Genetics.
How to fight chronic inflammation
St. Jude scientists led a study that identified a subset of immune cells. These cells may be key to treating chronic, debilitating inflammatory disorders.
The study focused on a family of helper T cells called Th17 cells. Th17 cells launch the immune response against fungal infection and other threats. The cells are also known to fuel inflammation.
Researchers identified a new subset of Th17 cells distinct from the conventional Th17 cells that drive chronic inflammation. These two types of Th17 cells have their own unique functions.
The St. Jude team showed that metabolism and a protein complex called mTORC1 play important roles in regulating Th17 function.
“Identification of this new Th17 subset opens new avenues for developing effective treatment of chronic inflammatory conditions,” said Hongbo Chi, PhD, of St. Jude Immunology.
This work was published in the journal Nature.
Controlling protein factories within cells
Booming construction occurs inside cells. This includes the regulation and assembly of different parts of cells. Scientists at St. Jude are learning about what controls the construction of protein-making factories called ribosomes.
Ribosomes are made inside a part of the cell called the nucleolus. A protein called nucleophosmin helps organize the nucleolus. This protein also regulates the construction of ribosomes.
To study this protein, the researchers used protein-containing droplets that mimic the liquid-like properties of the nucleolus.
“This approach showed that nucleophosmin works with a molecular partner called SURF6,” said Richard Kriwacki, PhD, of St. Jude Structural Biology. “Together, these partners adapt and control the fluid structure of the nucleolus as it assembles ribosomes.”
Understanding this process may help researchers develop targeted cancer treatments. The findings may also influence research on amyotrophic lateral sclerosis, or Lou Gehrig disease.
This work appeared in the journal Nature Communications.
Brain development findings have clinical applications
St. Jude researchers have discovered how two proteins interact to control hundreds of genes that build the developing human brain. The scientists found that the proteins UTX and 53BP1 link to activate the program by which the genes control the development of immature pluripotent stem cells into functioning neurons and brain structures.
The protein UTX was known as an epigenetic regulator of chromosomes in brain development, but until now the other proteins involved in the process were unknown. Epigenetic controls manage switching genes on or off to orchestrate development from generic cells to specialized cells like neurons.
The genome of thousands of individual genes is like data stored on a computer disk, but the epigenome is like a computer program that controls how stored data are read.
The findings have potential clinical implications because abnormalities in the UTX function cause defects in brain development such as the rare Kabuki syndrome and the brain tumor medulloblastoma.
The findings appeared in the journal Nature Neuroscience.
From Promise, Spring 2019