CNIO researchers discover new genetic errors that could cause 1 of the most deadly leukaemias

The sequencing of the acute dendritic cell leukaemia exome shows that more than half of patients display 'epigenetic' gene alterations

2013-10-23

(Press-News.org) Contact information: Nuria Noriega
comunicacion@cnio.es
Centro Nacional de Investigaciones Oncologicas (CNIO)
CNIO researchers discover new genetic errors that could cause 1 of the most deadly leukaemias The sequencing of the acute dendritic cell leukaemia exome shows that more than half of patients display 'epigenetic' gene alterations Acute dendritic leukaemia is a rare type of leukaemia, but one with the worst prognosis—the average patient survival rate is just 12-14 months—that is difficult to treat. Juan Cruz Cigudosa's team, from the Spanish National Cancer Research Centre's (CNIO) Molecular Cytogenetics Group, has for the first time sequenced the exome –the coding, or protein-generating, regions of the genome— of dendritic cell leukaemia.

The analyses, published in Leukemia, the world's leading journal in onco- haematology, uncover new genetic pathways that could revolutionise treatment guidelines for these patients.

'EPIGENETIC' GENES ARE ALTERED IN MOST CASES

For the first time in human leukaemias, scientists have described mutations in four genes (IKZF3, HOXB9, UBE2G2 and ZEB2) that have important cellular functions, such as gene regulation and cellular differentiation.

"In addition to these genes, we have found that more than half of the cases harbour mutations in epigenetic genes at diagnosis —those genes that introduce chemical modifications in the DNA— something that had never been observed in this type of leukaemia", says Cigudosa. "Therapies directed against these epigenetic genes already exist, so these patients could also benefit from them".

In summary, the genetic profile of acute dendritic cell leukaemia, currently treated as a lymphoid leukaemia, is similar to that of myeloid leukaemia. "These results suggests a change in the treatment guidelines for these patients, who were completely misplaced", says Juliane Menezes, the first author of the study.

According to Cigudosa, "this study is a clear example of the role of genomics in translational research being carried out by Spanish scientists, in general, and more specifically at CNIO".

To carry out this work, the authors analysed the exome of three patients diagnosed with dendritic cell leukaemia and validated the results using a panel of 38 genes and 25 additional patients (known as a targeted resequencing strategy), coming from 9 Spanish hospitals.

### This research was conducted in collaboration with CNIO's Bioinformatics Core Unit, led by David Pisano, the Pathology Services at the Marques de Valdecilla Hospital in Santander, led by Miguel Angel Piris, as well as several Spanish Genetics and Haematology Services.

Acknowledgements: the study has been supported by the Ministry of Economy and Competitiveness, the Carlos III Health Institute, the Spanish Association Against Cancer (AECC) and 'La Caixa' Foundation.

Reference article: Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm. Menezes J, Acquadro F, Wiseman M, Gómez-López G, Salgado RN, Talavera-Casañas JG, Buño I, Cervera JV, Montes-Moreno S, Hernández-Rivas JM, Ayala R, Calasanz MJ, Larrayoz MJ, Florensa L, Gonzalez-Vicent M, Pisano DG, Piris MA, Alvarez S, Cigudosa JC. Leukemia (2013). DOI: 10.1038/leu.2013.283

ELSE PRESS RELEASES FROM THIS DATE:

Imaging breast cancer with light

2013-10-23

Imaging breast cancer with light Netherlands researchers unveil their 'photoacoustic mammoscope,' a new device that could someday be used for routine breast cancer screenings ...

'Common courtesy' lacking among doctors-in-training

2013-10-23

'Common courtesy' lacking among doctors-in-training Johns Hopkins researchers say 'etiquette-based' communications needed to improve medical outcomes Johns Hopkins investigators have found that doctors-in-training are unlikely to introduce themselves fully ...

Study finds prenatal diagnosis and birth location may significantly improve neonatal HLHS survival

2013-10-23

Study finds prenatal diagnosis and birth location may significantly improve neonatal HLHS survival Multi-center study led by Texas Children's Hospital and Baylor College of Medicine HOUSTON – (Oct. 23, 2013) – A first-of-its-kind study led by Texas Children's ...

Neurotoxin effectively relieves bone cancer pain in dogs, Penn researchers find

2013-10-23

Neurotoxin effectively relieves bone cancer pain in dogs, Penn researchers find By the time bone cancer is diagnosed in a pet dog, it is often too late to save the animal's life. Instead, the goal of treatment is to keep the dog as comfortable and free ...

Gene-silencing strategy opens new path to understanding Down Syndrome

2013-10-23

Gene-silencing strategy opens new path to understanding Down Syndrome Genome-wide changes result from silencing extra chromosome, scientists report at ASHG 2013 The first evidence that the underlying genetic defect responsible for trisomy 21, also known ...

HIV elimination in South Africa could be achieved by current treatment policy

2013-10-23

HIV elimination in South Africa could be achieved by current treatment policy The current antiretroviral treatment policy in South Africa could lead to elimination of HIV within the country over the next 24 to 34 years, but a universal test and treat (UTT) ...

RNA signatures from suspected TB patients could form the basis of a diagnostic test

2013-10-23

RNA signatures from suspected TB patients could form the basis of a diagnostic test A set of RNA transcriptional signatures expressed in the blood of patients might provide the basis of a diagnostic test that can distinguish active tuberculosis (TB) from ...

Xpert MTB/RIF test may improve diagnosis of tuberculous meningitis in HIV-infected individuals

2013-10-23

Xpert MTB/RIF test may improve diagnosis of tuberculous meningitis in HIV-infected individuals Tuberculous meningitis (TBM) is a serious and often fatal illness that is difficult to diagnose particularly in resource-poor areas and is especially common ...

Delaying gratification, when the reward is under our noses

2013-10-23

Delaying gratification, when the reward is under our noses How can some people resist the attraction of immediate pleasures and pursue long-term goals, while others easily succumb and compromise their ultimate expectations? A recent study led by researchers at the Brain ...

Internet users more likely to engage in cancer-preventive behaviors

2013-10-23

Internet users more likely to engage in cancer-preventive behaviors PHILADELPHIA — Older men and women who used the internet were more likely to participate in screening for colorectal cancer, participate in physical activities, eat healthily, ...