Posts Tagged ‘children’

Study identifies gene network behind untreatable leukemia, possible treatment target

Scientists from the Cancer and Blood Diseases Institute (CBDI) at Cincinnati Children’s Hospital Medical Center report their results in a study posted online Sept. 4 by Cell Reports.

The specific forms of AML and MDS in the current study involve deletions on the arm of a specific chromosome in blood cells (del(5q). In patients with less aggressive forms of del(5q) MDS, the percentage of bone marrow blasts in their blood (the earliest, most immature cells of the myeloid cell line) is less than 5 percent. This means treatment prognosis for those patients typically is good, according to the study’s lead investigator, Daniel Starczynowski PhD, a researcher in the division of Experimental Hematology and Cancer Biology, part of the CBDI at Cincinnati Children’s.

“Unfortunately, a large portion of del(5q) AML and MDS patients have increased number of bone marrow blasts and additional chromosomal mutations,” Starczynowski said. “These patients have very poor prognosis because the disease is very resistant to available treatments such as chemotherapy and radiation. Finding new therapies is important and this study identifies new therapeutic possibilities.”

The researchers conducted their study in human AML/MDS cells and mouse models of del(5q) AML/MDS. They found that reduced expression of a certain gene in blood cells (miR-146a) led to activation of a molecular signaling network involving several components of NF-kB, one of which involved a protein called p62 — a critical regulator of cell metabolism, cellular remodeling and certain cancers.

Deletion of the miR-146a gene led to overexpression of p62, which caused sustained activation of what researchers identified as an NF-kB signaling network. This fueled the survival and aggressive growth of leukemic cells in cells and in mouse models.

Earlier attempts in previous studies to directly inhibit NF-kB (a key molecular facilitator to the leukemic process) have not proven successful, according to investigators on the current paper. So the authors performed follow-up laboratory tests to look for possible vulnerabilities to NF-kB and a potential workaround by targeting instead p62 within the NF-kB signaling network.

The researcher next tested inhibiting/knocking down p62 as an experimental treatment strategy in mouse models of leukemia and in human cells. The authors reported that targeting p62 prevented expansion of leukemic cells in mouse models and reduced the number of leukemia cell colonies by 80 percent in human AML/MDS cells.

Starczynowski stressed that significant additional research is needed to further verify the findings and learn more about the molecular processes involved. He also cautioned that laboratory results in mouse models do not necessarily translate to humans, and it isn’t known at this time how the findings might be directly applicable to clinical treatment.

source : http://www.sciencedaily.com/releases/2014/09/140904131603.htm

Guidelines can predict early menopause in child cancer survivors, giving hope for fertility

The criteria — developed in Edinburgh — will help to select which girls should be offered the opportunity to freeze some tissue from their ovaries for use in the future.

Doctors are optimistic that the frozen tissue could one day help young cancer survivors to have children of their own.

Some cancer treatments can affect female fertility by bringing on early menopause. Freezing samples of ovary tissue before patients start treatment is the only option to try to preserve their fertility.

At least 30 babies have been born from frozen ovarian tissue taken from adult women but the procedure remains unproven in girls and young women.

Taking the initial samples of ovaries to be frozen involves a surgical technique and is still relatively experimental. It is therefore crucial that doctors can accurately predict which patients are most likely to benefit and when it can be safely performed.

Guidelines were developed almost 20 years ago to select which girls should be offered the procedure, based on their age, type of cancer treatment and their chances of being cured of their cancer. Now that the girls are older, doctors are able to validate their predictions.

Researchers — led by the University of Edinburgh — validated the criteria by looking back at more than 400 girls with cancer who were under 18 years of age when diagnosed. They found that the criteria accurately predicted all but one of the patients who entered early menopause.

The study, funded by the Medical Research Council, is published in the journal Lancet Oncology.

The lead researcher is Professor Hamish Wallace of the University of Edinburgh’s Department of Child Life and Health and Consultant Paediatric Oncologist at the Royal Hospital for Sick Children (RHSC), where the research was carried out. He said: “Advances in lifesaving treatments mean that more and more young people with cancer are surviving the disease. Here we have an opportunity to help young women to have families of their own when they grow up, if they so choose.”

source : http://www.sciencedaily.com/releases/2014/08/140815102235.htm

Down syndrome: Behind the scenes of genetics, leukemia

A group of geneticists working in the Faculty of Medicine at the University of Geneva (UNIGE) focused for many years on the genetic characteristics of Down syndrome. They have sequenced the exome, a specific part of our genome, in a cohort of patients affected both by Down Syndrome and Acute Lymphoblastic Leukemia (DS-ALL), a type of cancer relative to the cells of the immune system in the bone marrow.

They were able to sketch an outline of the “genetic identity card” of this disease. They found that RAS, an important oncogene in many cancers, is involved in the tumorigenesis of one third of DS-ALL cases.

This work is being published in the latest issue of the journal Nature Communications.

source : http://www.sciencedaily.com/releases/2014/08/140808111735.htm