Saturday, October 22, 2011

Acquired genomic copy number aberrations

We all know by now that TP53 malfunction carries a dreadful prognosis in CLL, but there are relapsed and refractory cases that do not have anything ostensibly wrong with TP53. Is it possible to detect these and being pre-warned direct such patients into more effective treatments?

An attempt has been made in an article in Blood from September 15th. Acquired genomic copy number aberrations and survival in chronic lymphocytic leukemia.

The limitations of FISH are that it only gives infromation in the areas that are probed for - usually on chromosomes 11, 12, 13 and 17. The group at Ann Arbor have analyzed high-purity DNA isolated from FACS-sorted CD19(+) cells and paired CD3(+) or buccal cells from 255 patients with CLL for acquired genomic copy number aberrations (aCNAs) with the use of ultra-high-density Affymetrix SNP 6.0 arrays.

Overall, ≥ 2 subchromosomal aCNAs were found in 39% (100 of 255) of all cases analyzed, whereas ≥ 3 subchromosomal aCNAs were detected in 20% (50 of 255) of cases. With the use of multivariate analyses incorporating the most important prognostic factors in CLL together with SNP 6.0 array-based genomic lesion loads at various thresholds, they identified elevated CLL genomic complexity as an independent and powerful marker for the identification of patients with aggressive CLL and short survival. The only other marker to show up as of independent significance in the multivariate analysis was IGHV mutational status.

No comments: