Short communicationDeletion of 5q as a rare abnormality in chronic lymphocytic leukemia
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 GeneticsCitation 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.
A case of chronic lymphoblastic leukemia with an abnormal rare karyotype
2015, Comparative Clinical PathologyAn uncommon case of an adult with del(5)(q) in acute lymphoblastic leukemia
2012, Indian Journal of Human Genetics