Isochromosome 17q in Chronic Lymphocytic Leukemia

Abstract

In chronic lymphocytic leukemia (CLL), presence of acquired cytogenetic abnormalities may help to estimate prognosis. However, deletion of TP53 gene, which is associated with an aggressive course of the disease and poor prognosis along with a lack of response to treatment, is one of the alterations which may escape cytogenetic diagnoses in CLL. Thus, other techniques have emerged such as interphase fluorescence in situ hybridization (iFISH). Deletion of TP53 may but must not go together with the formation of an isochromosome i(17q); surprisingly this subgroup of patients was not in the focus of CLL studies yet. This study was about if presence of i(17q) could be indicative for a new subgroup in CLL with more adverse prognosis. As a result, TP53 deletion was detected in 18 out of 150 (12%) here studied CLL cases. Six of those cases (~33%) had the TP53 deletion accompanied by an i(17q). Interestingly, the cases with i(17q) showed a tendency towards more associated chromosomal aberrations. These findings may be the bases for follow-up studies in CLL patients with TP53 deletion with and without i(17q); it may be suggested that the i(17q) presents an even more adverse prognostic marker than TP53 deletion alone.

Figure 1

(a) Isochromosome 17q was detected initially by iFISH in this case; representative examples for heterozygote deletions of TP53 and #17 subtelomeric region 17p (subtel. 17pter) besides three signals for UNC13D and subtel. 17qter. Only 2 signals for centromere of chromosome 17 (D17Z1) and ATM gene on chromosome 11 were detected. (b) aCGH showed deletion of short arm and gain of long arm of chromosome 17 in case 3.

Figure 2

Here a scheme for the suggested procedures how to delineate an i(17q), if cytogenetics, MLPA, and iFISH are available.