Cancer genomics: Addressing treatment resistance in childhood acute lymphoblastic leukemia

December 20, 2016

In the third week of PLOS Medicine's ongoing special issue on cancer genomics, principal investigator Jules Meijerink of the Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands and colleagues seek to identify mechanisms underlying treatment resistance in children with T-cell acute lymphoblastic leukemia (T-ALL) by combining genomic DNA sequencing and chromosomal copy-number analyses, and suggest a new approach to therapy.

Treatment of childhood leukemia has improved markedly in recent decades, with long-term cure achieved in most patients who have access to modern, highly intensive treatment regimens. However, some patients develop resistance to the steroid drugs which are a key part of combination chemotherapy treatments, which results in poor clinical outcomes. As described in their Research Article, Meijerink and colleagues studied genetic changes in leukemic cells from pediatric T-ALL patients before treatment. The researchers found specific gene mutations affecting signaling inside cells, involving the interleukin 7 receptor and downstream molecules, that were associated with steroid resistance and adverse clinical outcome. Drugs designed to target individual signaling proteins were able to restore steroid sensitivity to primary leukemic cells from patients.

Discussing the research in an accompanying Perspective article, Steven Goossens and Pieter Van Vlierberghe conclude that "inhibition of MEK-ERK or PI3K/AKT/mTOR signaling could enhance steroid sensitivity in T-ALL and potentially improve patient outcomes, a notion that warrants investigation in future prospective clinical trials."
Research Article

Funding: YL was funded by Stichting Kinderen Kankervrij (; KiKa-2010-082). KC-B and WKS were funded by Stichting Kinderen Kankervrij (; KiKa-2008-029, KiKa-2013-116). EMV was funded by KWF Kanker Bestrijding (; EMCR-KWF-2010-4691). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: RCB and GJRZ are founders and shareholders of Netherlands Translational Research Center B.V. The other authors have declared that no competing interests exist.

Citation: Li Y, Buijs-Gladdines JGCAM, Canté-Barrett K, Stubbs AP, Vroegindeweij EM, Smits WK, et al. (2016) IL-7 Receptor Mutations and Steroid Resistance in Pediatric T cell Acute Lymphoblastic Leukemia: A Genome Sequencing Study. PLoS Med 13(12): e1002200. doi:10.1371/journal.pmed.1002200

Author Affiliations:
Department of Pediatric Oncology/Hematology, Erasmus Medical Center/Sophia Children's Hospital, Rotterdam, The Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Department of Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands
Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands
Research Institute Children's Cancer Center Hamburg, Hamburg, Germany
Clinic of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Co-operative Study Group for Childhood Acute Lymphoblastic Leukemia, Hamburg, Germany
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
Netherlands Translational Research Center, Oss, The Netherlands


Perspective Article

Funding: The authors received no funding for this work.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Goossens S, Van Vlierberghe P (2016) Overcoming Steroid Resistance in T Cell Acute Lymphoblastic Leukemia. PLoS Med 13(12): e1002208. doi:10.1371/journal.pmed.1002208

Author Affiliations:
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
Department for Biomedical Molecular Biology, Ghent University, Ghent, Belgium
Cancer Research Institute Ghent (CRIG), Ghent, Belgium



Related Pediatric Articles from Brightsurf:

Racial disparities in pediatric diabetes treatment
Type 1 diabetes (T1D) is the third most common pediatric chronic disease in the United States, and the risk of the disease has risen sharply in non-Hispanic Black (NHB) children in the last 20 years, data show.

Pediatric surgeon establishes first-ever guidelines for pediatric opioid prescribing
In addition to adults, opioid addiction and misuse affects the pediatric population.

Improving the transition from pediatric to adult rheumatology care
As children with chronic rheumatic illnesses age, it's important that they experience a smooth transition from pediatric to adult care.

How COVID-19 affects pediatric patients
New insights into the clinical and epidemiological characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) could facilitate early identification and intervention in suspected patients, according to a study publishing on June 16, 2020 in the open-access journal PLOS Medicine by Xihui Zhou of the First Affiliated Hospital of Xi'an Jiaotong University, China and colleagues.

COVID-19 associated with dramatic decline in ED use by pediatric asthma patients
The number of patients visiting the emergency department (ED) for asthma treatment dropped by 76% in the first month of the COVID-19 pandemic, according to a new study by researchers at Children's Hospital of Philadelphia (CHOP).

What pediatric health care clinicians need to know
Information on the coronavirus disease 2019 pandemic that is useful for pediatric clinicians is in this article.

Getting to the heart of epinephrine use in pediatric cardiac arrest patients
The effectiveness of epinephrine treatment during resuscitation of adult patients with cardiac arrest is generally promising, but little is known about its effects in pediatric patients.

Pediatric cancers: Why some forms of leukemia only affect children
Acute myeloid leukemia (AML) mainly affects children, with the prognosis often being poor despite several decades of research into more effective treatments.

Researchers refine guidelines for pediatric brain injuries
There are no guideliInnes on whether a noninvasive method of measuring carbon dioxide from patients' exhalations, known as end-tidal capnography, is as effective as drawing blood through a child's artery.

Is obesity associated with risk of pediatric MS?
A single-center study of 453 children in Germany with multiple sclerosis (MS) investigated the association of obesity with pediatric MS risk and with the response of first-line therapy in children with MS.

Read More: Pediatric News and Pediatric Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to