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Researchers discover new genetic errors that could cause deadly leukemia

Date:
October 23, 2013
Source:
Centro Nacional de Investigaciones Oncologicas (CNIO)
Summary:
Acute dendritic leukemia is a rare type of leukemia, but one with the worst prognosis -- the average patient survival rate is just 12-14 months, and it is difficult to treat. Now researchers have, for the first time, sequenced the exome of dendritic cell leukemia. The analyses uncover new genetic pathways that could revolutionize treatment guidelines for these patients.
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Acute dendritic leukemia is a rare type of leukemia, 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 leukemia.

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 leukemias, 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 leukemia," 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 leukemia, currently treated as a lymphoid leukemia, is similar to that of myeloid leukemia. "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 leukemia 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.


Story Source:

The above post is reprinted from materials provided by Centro Nacional de Investigaciones Oncologicas (CNIO). Note: Materials may be edited for content and length.


Journal Reference:

  1. J Menezes, F Acquadro, M Wiseman, G Gómez-López, R N Salgado, J G Talavera-Casañas, I Buño, J V Cervera, S Montes-Moreno, J M Hernández-Rivas, R Ayala, M J Calasanz, M J Larrayoz, L F Brichs, M Gonzalez-Vicent, D G Pisano, M A Piris, S Álvarez, J C Cigudosa. Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm. Leukemia, 2013; DOI: 10.1038/leu.2013.283

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Centro Nacional de Investigaciones Oncologicas (CNIO). "Researchers discover new genetic errors that could cause deadly leukemia." ScienceDaily. ScienceDaily, 23 October 2013. <www.sciencedaily.com/releases/2013/10/131023125707.htm>.
Centro Nacional de Investigaciones Oncologicas (CNIO). (2013, October 23). Researchers discover new genetic errors that could cause deadly leukemia. ScienceDaily. Retrieved July 4, 2015 from www.sciencedaily.com/releases/2013/10/131023125707.htm
Centro Nacional de Investigaciones Oncologicas (CNIO). "Researchers discover new genetic errors that could cause deadly leukemia." ScienceDaily. www.sciencedaily.com/releases/2013/10/131023125707.htm (accessed July 4, 2015).

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