13Q DELETION IS PREDOMINANT CYTOGENETIC ABERRATION NEWLY AQUIRED DURING CHRONIC LYMPHOCYTIC LEUKEMIA COURSE IRRESPECTIVE OF DISEASE ACTIVITY AND TREATMENT STATUS

Background
In Chronic lymphocytic leukemia (CLL) four recurrent cytogenetic aberrations with different prognostic impact are routinely tested: deletions 11q, 13q, 17p and trisomy 12. Their prognostic impact is generally described using Dohner’s hierarchy: del17p > del 11q > tris 12 > normal > del 13q. The aberrations are usually tested once at the diagnosis but their spectra can change during disease evolution.

Aims
Repeated analysis of the four recurrent CLL cytogenetic aberrations was aimed to monitor the changes in aberration distribution in the different disease stages.

Methods
Four common cytogenetic aberrations (deletions 11q, 13q, 17p, and trisomy 12) were detected using interphase FISH analysis. 

Results

Based on the disease course and therapy administration, CLL patients were stratified into two groups: (A) patients with indolent disease – 16 % (52/335), no treatment required, median follow-up 75 months; (B) patients with progressive disease requiring therapy intervention either after an inactive phase (56 %; 186/335; median time to first treatment 35 months; median follow-up 74 months), or soon after diagnosis (28 %; 97/335; median time to first treatment 14 months, median follow-up 54 months).

In total, newly acquired cytogenetic aberration was detected in 33 % (109) from 335 repeatedly tested patients. In the indolent group A, 23 % (12/52) of patients gained a new aberration during follow-up. In almost all cases (92 %; 11/12) the newly acquired aberration was deletion 13q. In the progressive group B, patients were tested repeatedly before the first therapy and during relapse where possible. 11 % (30/283) of patients gained a new aberration already before therapy - 20 % (6/30) at inactive phase and 80 % (24/30) at active phase of CLL. Del 13q comprised 83% (5/6) of aberrations gained at inactive phase. The distribution of aberrations gained at active phase of CLL was following: del 13q in 63 % (15/24), del 17p in 17 % (4/24), del 11q in 13 % (3/24), and tris 12 in 7 % (2/24) of cases. 71 % (200/283) of CLL patients were tested again in progression after therapy. New chromosomal aberration was detected in 34 % (67/200) of cases: del 13q in 61 % (41/67), del 17p in 28 % (19/67), del 11q in 16 % (11/67), and tris 12 in 1 % (1/67).

Summary

In our study we showed that 33 % of repeatedly tested patients acquired additional cytogenetic aberrations during the CLL course. The most frequently acquired aberration was 13q deletion (66 %). Regarding the disease activity, deletion 13q comprised 92 % newly acquired aberrations among patients with indolent CLL without clinical manifestation of the disease progression. Surprisingly, 13q deletion comprised 60 % of all aberrations acquired before therapy and 61 % of all aberrations acquired after therapy also in the group with progressive disease. Our data suggests that the proportion of the deletion 13q among newly acquired aberrations appears independent on the disease activity and therapy intervention. In contrary, 17p deletion acquisition increases with disease activity and foregoing therapy, 13 % before vs. 28 % cases after treatment in progressive group.

Supported by: IGA MZCR NT13519, IGA MZCR NT13493, CZ.1.05/1.1.00/02.0068, CZ.1.07/2.3.00/30.0009, NGS-PTL/2012-2015/no.306242, MSMT-CR (2013-2015, no.7E13008)

Keyword(s): B cell chronic lymphocytic leukemia, Cytogenetic abnormalities, FISH

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