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Deletion of 5q as a rare abnormality in chronic lymphocytic leukemia

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Abstract

Deletions of the long arm of chromosome 5 [del(5q)] are frequent chromosome aberrations with known prognosis in myelodysplastic syndromes and acute myeloid leukemia (AML). However, in chronic lymphocytic leukemia (CLL), they are rare and have been reported only as karyotypic results without known prognosis. In the present study, we report a novel conventional and molecular cytogenetic study of two CLL patients carrying interstitial del(5q) in order to contribute to the identification of rare recurrent aberrations and their prognostic impact in CLL. Karyotypic and fluorescence in situ hybridization analysis that used probes for the most common aberrations of CLL demonstrated that del(5q) was the sole chromosome abnormality in both patients at the time of diagnosis. None of these patients had a history of exposure to chemotherapy or radiotherapy. Both patients had disease that was still staged as Binet A at 28 and 18 months after diagnosis, respectively, without receiving any therapy because of their good clinical condition. Therefore, it could be suggested that del(5q) may not be associated with an adverse prognosis in CLL and is not related with therapy-induced chromosome changes. Further studies are required to elucidate the prognostic value of these deletions in more CLL patients, which could be advisable for prognostic and therapeutic purposes, as well as to identify candidate genes that may potentially play a role in the pathogenesis of CLL.

Introduction

Chronic lymphocytic leukemia (CLL) is the most common leukemia of elderly adults in Western countries, marked by a clonal expansion of mature B lymphocytes in both the lymphoid organs and bone marrow [1]. Cytogenetic analysis is important in diagnosing CLL and represents an independent predictor of prognosis, treatment response, and follow-up. Furthermore, it constitutes a valuable research tool: it can serve as a starting point for further investigations because it reveals chromosomal rearrangements across the whole genome.

However, conventional cytogenetic analysis in CLL is hampered by the low mitotic activity of CLL cells in vitro and their poor response to the traditionally used mitogens [2]. New combinations of mitogens, such as the immunostimulatory CpG-oligonucleotide DSP30 combined with interleukin (IL)-2, have only recently been reported to identify aberrations in 81–83% of cases [2]. Moreover, even though fluorescence in situ hybridization (FISH) techniques enable the detection of genomic aberrations in more than 80% of CLL patients, they provide only partial information confined to the chromosomal regions examined [2], [3]. Consequently, the panel of chromosome abnormalities and their prognostic significance in CLL have not yet been determined; the prognostic importance of less frequent or rare recurrent aberrations is controversial or remains unknown.

Given the importance of cytogenetic abnormalities in CLL, and in order to contribute to the identification of rare recurrent aberrations and their prognostic impact in CLL, we report a conventional and molecular cytogenetic study of two CLL cases with an interstitial deletion of the long arm of chromosome 5 [del(5q)] as the sole abnormality.

Section snippets

Patient 1

A 58-year-old woman with absolute lymphocytosis since 2000 was diagnosed with B-CLL in October 2007. At the time of diagnosis, physical examination and a computed tomographic scan revealed lymphadenopathy but no signs of splenomegaly. Peripheral blood examination showed white blood cell count (WBC) 16.17 × 109/L (56% lymphocytes), hemoglobin (Hb) 149 g/L, and platelet count (PLT) 277 × 109/L. Bone marrow biopsy results revealed 23% interstitial infiltration by small lymphocytes. Flow cytometric

Chromosome studies

In patient 1, chromosome studies were performed on unstimulated bone marrow cells that were cultured for 24 and 48 hours, and on stimulated cells with 12-O-tetradecanoylphorbol-19-acetate (TPA) that were cultured for 96 hours at diagnosis. A second chromosomal analysis was carried out in February 2009 on peripheral blood cells. A culture with the oligonucleotide DSP30 plus IL-2 was additionally set up along with the TPA as a new and promising combination of CLL mitogens.

In patient 2, chromosome

Cytogenetics

Chromosome analysis of bone marrow cells of patient 1 revealed an abnormal clone containing an interstitial del(5q), with breakpoints at chromosomal regions q15 and q31, in 7 of the 26 metaphases evaluated. The abnormal clone was present in all cultures. The karyotype was described as 46,XX,del(5)(q15q31)[7]/46,XX[19]. In the second chromosomal analysis of patient 1, this time performed on peripheral blood cells, chromosome analysis was feasible in only 20 metaphases because of the low mitotic

Discussion

Deletions of the long arm of chromosome 5 as sole abnormalities or together with other chromosome changes are frequent chromosome aberrations with known prognosis in MDS and AML. However, little can be said about del(5q) in CLL because it has almost always been found together with other aberrations in some rare cases of CLL, hairy cell leukemia, Sézary syndrome, and prolymphocytic leukemia [4].

A systematic review of the literature since 1984 revealed only 13 CLL cases carrying interstitial

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Cited by (6)

  • Chronic lymphocytic leukemia: A clinical and molecular heterogenous disease

    2013, Cancer Genetics
    Citation Excerpt :

    Several other recurrent genomic aberrations have been described in CLL, such as total or partial trisomy 3, trisomy 8, trisomy 18, and trisomy 19—changes that lead to gains of 2p24–25, 3q26–27, and 8q24. Two cases of patients with a deletion of the long arm of chromosome 5 (5q–) and no other cytogenetic abnormalities have been reported; these patients were Binet stage A at 18 and 28 months after diagnosis, which suggests that this aberration may be related to an indolent course (93). These aberrations are rare in CLL and their prognostic significance is unknown.

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