Stories about: Dana-Farber Boston Children’s

GALLERY: Forecasting the future of pediatric hematology/oncology

Title image for pediatric hematology/oncology predictionsRecently, the annual ASPHO (American Society for Pediatric Hematology/Oncology) meeting brought together more than 1,100 pediatric hematologists and oncologists, including a team from the Dana-Farber/Boston Children’s Cancers and Blood Disorders Center. Some of the delegates from Dana-Farber/Boston Children’s included:

Based on their discussions with their peers, these are their key takeaways from the meeting:

Read Full Story | Leave a Comment

Naturally-occurring molecule in tree leaves could treat anemia, other iron disorders

Hinoki cypress

“Without iron, life itself wouldn’t be feasible,” says Barry Paw, MD, PhD. “Iron transport is very important because of the role it plays in oxygen transport in blood, in key metabolic processes and in DNA replication.”

Although iron is crucial to many aspects of health, it needs the help of the body’s iron-transporting proteins. Which is why new findings reported in Science could impact a whole slew of iron disorders, ranging from iron-deficiency anemia to iron-overload liver disease. The team has discovered that a small molecule found naturally in Japanese cypress tree leaves, hinokitiol, can transport iron to overcome iron disorders in animals.

The multi-institutional research team is from the University of Illinois, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Brigham and Women’s Hospital and Northeastern University. Paw, co-senior author on the new paper and a physician at Dana-Farber/Boston Children’s, and members of his lab demonstrated that hinokitiol can successfully reverse iron deficiency and iron overload in zebrafish disease models.

“Amazingly, we observed in zebrafish that hinokitiol can bind and transport iron inside or out of cell membranes to where it is needed most,” says Paw.

This gives hinokitiol big therapeutic potential.

Read Full Story | Leave a Comment

Science then & now: Progress that you can see

Click and drag to compare and contrast archive photos from the lab with current-day images of research at Boston Children’s Hospital.

Then, 1986: Stuart H. Orkin, MD, examines the DNA sequence of a gene.

Now, 2017: Today, Orkin is associate chief of Hematology/Oncology and chairman of Pediatric Oncology at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center (DF/BC). In this photo, he examines a rendering of a gene regulatory molecule’s structure. Orkin’s lab investigates gene regulation of stem cell development, genetic vulnerabilities to cancer and gene and other therapies for treating hemoglobin disorders. 

Read Full Story | Leave a Comment

New dataset reveals the individuality of childhood cancers

Tumor cells, like the ones pictured here, have unique genetic profiles across childhood cancers
Imaging of tumor cells. A new dataset, one of the largest of its kind, contains the genomic profiles of 1,215 pediatric tumors.

Childhood cancers are rare and account for about one percent of U.S. cancer diagnoses. They differ from adult tumors in that they often arise from many more diverse kinds of cells, including embryonal tissues, sex-cord stromal cells of the ovary or testis, the brain’s neural and glial cells and more.

Yet although improved tumor detection and treatment have increased survival rates for many different cancer subtypes, more than 1,900 children across the U.S. still lose their battle each year.

A new dataset — comprising the genomic profiles of a huge array of pediatric tumors — could help change that.

Read Full Story | Leave a Comment

Discovering a rare anemia in time to save an infant’s life

Illustration of the erythropoietin hormone. A newly-discovered genetic mutation, which switches one amino acid in EPO's structure, resulted in two cases of rare anemia.
An illustration showing the structure of a cell-signaling cytokine called erythropoietin (EPO). It has long been thought that when EPO binds with its receptor, EPOR, it functions like an on/off switch, triggering red blood cell production. New findings suggest that this process is more nuanced than previously thought; even slight variations to cytokines like EPO can cause disease.

While researching a rare blood disorder called Diamond-Blackfan anemia, scientists stumbled upon an even rarer anemia caused by a previously-unknown genetic mutation. During their investigation, the team of scientists — from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, the Broad Institute of Harvard and MIT and Yale University — had the relatively unusual opportunity to develop an “on-the-fly” therapy.

As they analyzed the genes of one boy who had died from the newly-discovered blood disorder, the team’s findings allowed them to help save the life of his infant sister, who was also born with the same genetic mutation. The results were recently reported in Cell.

“We had a unique opportunity here to do research, and turn it back to a patient right away,” says Vijay Sankaran, MD, PhD, the paper’s co-corresponding author and a principal investigator at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. “It’s incredibly rewarding to be able to bring research full circle to impact a patient’s life.”

Read Full Story | Leave a Comment

Mining similarities in pediatric and canine bone cancer to help both children and pets

dogs aid fight against osteosarcoma

In March 2016, Ollie, a therapy dog at Boston Children’s Hospital, paid a bedside visit to 7-year-old Carter Mock. The pug and the boy had something in common: Both had lost limbs to the bone cancer osteosarcoma. Ollie’s left front leg had been amputated at the shoulder, while Carter had just had a new knee fashioned from his ankle in a procedure called rotationplasty.

Biologically, the osteosarcoma that dogs develop is remarkably similar to osteosarcoma in children and youths. The tumors develop primarily in the long bones, and the spread of tumor cells to the lungs represents the most significant threat and challenge. Similar chemotherapy agents are used in both dogs and human patients to kill residual cancer cells. Researchers are now mining these similarities in a quest for new treatments to benefit pets and people alike.

Read Full Story | Leave a Comment

Rare blood disorder sideroblastic anemia slowly reveals its genetic secrets

congenital sideroblastic anemia
Regardless of the gene, all patients with sideroblastic anemia have sideroblasts: red blood cell precursors with abnormal iron deposits in mitochondria, shown here ringing the cell nucleus. (Paulo Henrique Orlandi Mourao/Wikimedia)

A decade ago, Brooks McMurray’s routine check-up was anything but routine. The suburban Boston boy’s spleen was enlarged. His red blood cell count was low and the cells were very small and very pale, which suggested a serious iron deficiency anemia. The family pediatrician referred McMurray, now a 19-year-old college freshman, to Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.

There hematologists discovered the boy had unexpectedly high iron levels. Together with pathologist Mark Fleming, MD, DPhil, they solved the mystery. McMurray has congenital sideroblastic anemia, an inherited blood disorder so rare that fewer than 1,000 cases have been reported worldwide. Iron was getting stuck in the wrong place in the precursor red blood cells developing in his bone marrow.

Read Full Story | Leave a Comment

Pediatric brain tumor genomics arrives, as the need for new therapies grows

Allison was the first pediatric brain tumor patient in the world to receive a treatment targeting the BRAF mutation, originally developed to treat adults with melanoma who have the same mutation.

Precision cancer medicine – the vision of tailoring diagnosis and treatments to a tumor’s genetic susceptibilities – is now ready to impact the care of a majority of children with brain tumors. The molecular “signatures” of brain tumors were first characterized in 2002 in a study led by researchers at Boston Children’s Hospital. This has led to the creation of new tumor subgroups and changes in cancer treatment: For example, a current clinical trial is testing the anti-melanoma drug dabrafenib in a variety of brain tumors with the same BRAF mutation – including metastatic anaplastic astrocytoma and low-grade glioma.

In the largest study of its kind to date, investigators at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center genetically tested more than 200 brain tumor samples. They found that many had genetic irregularities that could guide treatment, in some cases with approved drugs or agents being evaluated in clinical trials.

The findings, reported online today by the journal Neuro-Oncology, also demonstrate that testing pediatric brain tumor tissue for genetic abnormalities is clinically feasible.

Read Full Story | Leave a Comment

BCL11A-based gene therapy for sickle cell disease passes key preclinical test

sickle cell gene therapy coming
(unsplash/Pixabay)

Research going back to the 1980s has shown that sickle cell disease is milder in people whose red blood cells carry a fetal form of hemoglobin. The healthy fetal hemoglobin compensates for the mutated “adult” hemoglobin that makes red blood cells stiffen and assume the classic “sickle” shape.

Normally, fetal hemoglobin production tails off after birth, shut down by a gene called BCL11A. In 2008, researchers Stuart Orkin, MD, and Vijay Sankaran, MD, PhD, at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center showed that suppressing BCL11A could restart fetal hemoglobin production; in 2011, using this approach, they corrected sickle cell disease in mice.

Now, the decades-old discovery is finally nearly ready for human testing — in the form of gene therapy. Today in the Journal of Clinical Investigation, Dana-Farber/Boston Children’s researchers report that a precision-engineered gene therapy vector suppressing BCL11A production overcame a key technical hurdle.

Read Full Story | Leave a Comment

Treating relapsed child leukemia by matching therapy to the mutations

next generation sequencing cancer drugs child leukemia
(Bainscou / National Cancer Institute / Wikimedia Commons)

Although current treatments can cure 80 to 90 percent of cases, acute lymphoblastic leukemia (ALL) remains the second leading cause of cancer deaths in children. Patients with a resistant form of the disease, who relapse following successful treatment or who have other high risk features have few treatment options. Acute myeloid leukemia (AML) is also difficult to treat in children.

In a first-of-its-kind study, investigators at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center are testing precision cancer medicine in children and young adults with relapsed or high-risk leukemias. The goal is to determine whether powerful next-generation DNA sequencing can spot mutations or genetic changes in leukemia cells that can be targeted by cancer drugs.

Read Full Story | Leave a Comment