Trisomy 8q due to i(8q) or der(8) t(8;8) is a frequent lesion in T‐prolymphocytic leukaemia: four new cases and a review of the literature

Abstract

Cytogenetic abnormalities found in four cases of T-cell prolymphocytic leukaemia (T-PLL) are described. An isochromosome 8q was found in three patients and a t(8;8) in one. In the four cases, karyotypes were complex and showed a high degree of instability. In addition, we reviewed 27 published cases of cytogenetically studied T-PLL. On the whole, the most frequently recurring anomalies in T-PLL are 14q lesions with nonrandom breakpoints, inversion (14)(q11q32) or tandem translocations (14;14) (not seen in any of our cases) and trisomy for 8q. mainly due to i(8q), found in more than 40% of patients each. Similar structural anomalies were found almost as frequently among the 23 cytogenetically studied cases of so-called T-chronic lymphocytic leukaemia (T-CLL) reported prior to 1989. It is now accepted that the T-cell counterpart of B-CLL either does not exist or is exceedingly rare and thus previously reported cases of T-CLL sharing the chromosomal characteristics of T-PLL may well have been misdiagnosed examples of T-PLL. Isochromosomes 8q are exceptionally found in other types of haematological malignancies. However, i(8q) could not be shown to be the primary lesion in any case in T-PLL and the role of trisomy for 8q, as well of the associated monosomy 8p, is entirely unknown.

A complex pattern of recurrent chromosomal losses and gains in T‐cell prolymphocytic leukemia

“…Deletions of 12p have also been found in T-PLL, using FISH and LOH methods, with a frequency of 43% (Salomon-Nguyen et al, 1998;Hetet et al, 2000). Finally, recurrent deletions or translocations of chromosome arms 6q, 13q, 17p, and monosomy 22 have occasionally been reported by standard cytogenetics or FISH analyses (Matutes et al, 1991;Mossafa et al, 1994;Rosenwald et al, 1999).…”

“…It is typically characterized by a large tumoral mass and an aggressive clinical course with a short survival (Matutes et al, 1991;Garand et al, 1998). Cytogenetic studies of T-PLL reported complex karyotypes with some recurrent chromosomal abnormalities (Brito-Babapulle et al, 1987;Matutes et al, 1991;Heinonen et al, 1994;Mossafa et al, 1994;Maljaie et al, 1998;Salomon-Nguyen et al, 1998). The Xq28 or the 14q32.1 regions are involved in translocations or inversions with the TCRA/D at 14q11.…”

“…Unbalanced rearrangements of chromosome 8 have been reported in 40% to 80% of the patients. They are i(8)(q10), t(8;8)(p12;q11), or translocations involving 8p and other chromosomal partners, leading to trisomy 8q and/or monosomy 8p (Mossafa et al, 1994;Maljaie et al, 1998). More recently, recurrent losses of the 11q21-q23 region have been reported using fluorescence in situ hybridization (FISH) and loss of heterozygozity (LOH) analysis, and biallelic inactivation of the ATM gene was demonstrated in virtually all the sporadic T-PLLs, demonstrating that ATM has a tumor suppressor gene function (Stilgenbauer et al, 1997;Vorechovsky et al, 1997;Stoppa-Lyonnet et al, 1998Yuille et al, 1998).…”

Abnormalities of the short arm of chromosome 12 in T cell prolymphocytic leukemia

“…7,9-14 Chromosomes 14, 8, 6, 11 and X are among the most frequently involved, particularly rearrangements of bands 14q11 and 14q32, isochromosome 8q, 6q and 11q abnormalities, and t(X;14)(q28;q11). In view of the current data, rearrangements of chromosome 12p 7,10 should now be added to the list of the abnormalities associated with T-PLL. By performing FISH studies on 12p in three patients with T-PLL, rearrangements were detected including markers in two patients (A and C).…”

“…4 More recently, the question of the relationship between Sézary cell leukemia and T-PLL has been addressed. 5,6 Among the various chromosomal abnormalities described in T-PLL, rearrangements of chromosomes 14,8,6, 11 and X occurred most frequently 7 and association of several anomalies in the same patient often resulted in complex karyotypes.…”