Researchers discover new genetic errors that could cause one of the most deadly leukaemias

October 23, 2013

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 for these patients.

'Epigenetic' genes are altered in most cases

For the first time in human leukaemias, scientists have described mutations in four (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 . "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 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.

Explore further: Researchers link cancer to failures in chromosome protection for the first time

More information: 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

Related Stories

Researchers link cancer to failures in chromosome protection for the first time

March 19, 2013
A study published today in the journal Nature Genetics explores a new mechanism that may contribute to the development of several tumours, including Chronic Lymphocytic Leukaemia, a type of cancer that affects more than a ...

Rare leukaemia survival-rate breakthrough

August 13, 2013
A pioneering genetic study means that children with a rare subtype of leukaemia have 75% less chance of their leukaemia recurring.

Non-infiltrating bladder cancer exome sequenced

October 13, 2013
Bladder cancer represents a serious public health problem in many countries, especially in Spain, where 11,200 new cases are recorded every year, one of the highest rates in the world. The majority of these tumours have a ...

Protein that takes care of our DNA is critical to leukaemia cell survival

April 5, 2013
A protein – already known to be involved in a cell's response to stress – called Tetratricopeptide repeat domain 5 (TTC5) is critical to the development of acute myeloid leukaemia (AML), according to a new Cancer Research ...

Missing immune response may prove a vital link for new leukaemia treatments

September 20, 2013
(Medical Xpress)—Patients suffering from leukaemia could have their immune system engineered to fight the disease, after scientists at the University of Birmingham discovered that they lacked an immune response to a certain ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.