Clonal Evolution including 14q32/IGH translocations in CLL: analysis of clinicobiologic correlations in 105 patients

July 27, 2011

BlankClonal Evolution including 14q32/IGH translocations in Chronic Lymphocytic

Leukemia: analysis of clinicobiologic correlations in 105 patients.

C Francesco, R Lara, S Olga, D Giulia, C Francesca, M Sara, C , S Elena, D

, AE Abbas, B Antonella, T , C , and RG Matteo

Leuk Lymphoma, July 19, 2011;

Abstract To better define the significance of clonal evolution (CE) including

14q32 translocations involving the immunoglobulin heavy chain gene (IGH) in

chronic lymphocytic leukemia (CLL), 105 patients were analyzed sequentially by

fluorescence in situ hybridization (FISH) with the following panel of probes:

13q14/D13S25, 11q22/ATM, 17p13/TP53, #12-centromere and 14q32/IGH break-a-part

probe. CE was observed in 15/105 patients after 24-170 months (median 64).

Recurring aberrations at CE were 14q32/IGH translocation in 7 patients; other

aberrations were 17p- 11q-, biallelic 13q-, and 14q32 deletion. CE was detected

in 15/58 pre-treated patients; to the contrary none of 47 untreated patients

developed CE (p<0.0001). In two cases the appearance of 14q32/IGH translocation

was first detected in the bone marrow (BM) or in the lymph node (LN) and 13-58

months later in the peripheral blood (PB). ZAP70+ and high risk cytogenetics

predicted for the occurrence of CE with borderline statistical significance

(p=0.055 and 0.07, respectively). A shorter time to first treatment (TTT) and

time to chemorefractoriness (TTCR) were noted in 15 patients with CE when

compared to patients without CE (TTT: 35 vs 71 months, p=0.0033 and TTCR: 34 vs

86 months, 0.0046, respectively). Survival after the development of CE was 32

months (standard error 8,5). We arrived at the following conclusions: i)

14q32/IGH translocation may represent one of the most frequent aberrations

acquired during the natural history of CLL and, ii) it may be detected earlier

in BM or LN samples; iii) CE including 14q32/IGH translocation occur in

pre-treated patients with short TTT and TTCR; iii) survival after CE is

relatively short.

PMID: 21767243

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