Del(6q) in Chronic lymphocytic leukaemia (CLL)

2020-01-01   Liliya Grahlyova , Lubomir Mitev 

1.Military Medical Academy, Department of Cytogenetics and Molecular Biology, Sofia, Bulgaria, cytogen.vma@abv.bg

Abstract

Review on deletion 6q in chronic lymphocytic leukaemia

Clinics and Pathology

Disease

Chronic Lymphocytic Leukemia

Note

The deletions of the long arm of chromosome 6 are nonrandom cytogenetic anomalies found in 3 to 7% of cases with chronic lymphocytic leukemia (CLL). To date 163 CLL cases with 6q- are reported. These chromosome anomalies represent a highly heterogeneous group that includes 6q deletions of different lengths and locations. However, the deletion segments overlap some of the bands in 6q and most frequently 6q21, which suggests that in this chromosomal band are located genes or gene responsible for the molecular pathogenesis in a considerable number of cases with 6q- anomaly.

Epidemiology

The deletion of 6q is found in 163 cases with CLL (6% of all CLL cases with an abnormal karyotype). Sex ratio of the cases with 6q- is significantly unbalanced, near M:F=2.3:1. The anomaly is observed predominantly in older patients (average age 62.5 years; range 27-90).

Clinics

The 6q- anomaly is characterized with atypical lymphocyte morphology, CD38 positivity, more extensive lymphadenopathy, and intermediate incidence of IgVH somatic hypermutation (Cuneo A et al., 2004). In cases with 6q deletions have also been found significantly lower hemoglobin concentration, and significantly higher mean age, percent of peripheral prolymphocytes and level of serum lactate dehydrogenase compared with patients without 6q deletion (Stilgenbauer S et al., 1999: Welson MM et al., 2012).

Treatment

Cases of CLL with deletion of 6q have been shown to require a more demanding treatment regimen (Tsimberidou AM et al., 2007).

Prognosis

It have been suggested that CLL with 6q- comprise an intermediate-risk group and is predictive of shorter survival (Tsimberidou AM et al., 2007, Cuneo et al., 2004 ).

Cytogenetics

Cytogenetics morphological

Conventional cytogenetic analysis The 6q- anomaly is described in 92 cases as a terminal deletion and in 71 as an interstitial deletion.
The terminal 6q- deletions included the following variants: del(6)(q12) - 2 cases (Brejcha et al., 2014; Mayr et al., 2005), del(6)(q13) - 4 cases (Cuneo et al., 2004; Del Giudiceet al., 2018; Li et al., 2016; Wawrzyniak et al., 2014), del(6)(q14) - 3 cases (Hernandes et al., 1997; Li et al., 2012; Vandenberghe et al., 1992), del(6)(q15) -14 cases (Chena et al., 2003; Cuneo et al., 2004; Fleischman et al., 1989; Haferlach et al., 2007; Juliusson et al., 1985; Lewin et al., 1988; Merup et al., 1994; Reddy, 2006; Travella et al., 2013; Van Roosbroeck et al., 2016; Yunis et al., 1984), del(6)(q16) - 4 cases (Andreieva et al., 2017; Brejcha et al., 2014; Coignet et al., 1996; Vandenberghe et al., 1992), del(6)(q21) - 25 cases (Bernues et al., 2014; Campioni et al., 2012; Chena et al., 2003; Cuneo et al., 2004; Del Giudice et al., 2018; Dicker et al., 2006; Fleischman et al., 1989; Gardiner et al., 1997; Huh et al., 2007; Huh et al., 2011; Lu et al., 2010; Mayr et al., 2006; Offit et al., 1994; Pittman & Catovsky, 1984; Ripolles et al., 2006; Ross & Stockdill 1987; Schlette et al., 2005; Speaks et al., 1992; Travella et al., 2013; Vandenberghe et al., 1992; Wawrzyniak et al., 2014), del(6)(q22) - 2 cases (Nowell et al., 1988; Speaks et al., 1987), del(6)(q23) - 13 cases (Bloomfield et al., 1983; Callet-Bauchu et al., 1996; Crossen et al., 1987; Cuneo et al., 2002; Jarosova et al., 2010; Juliusson et al., 1988; Karakosta et al., 2010; Merup et al., 1994; Pittman & Katovsky, 1984; Sole et al., 1997; Woessner et al., 1996), del(6)(q24) - 6 cases (Andreieva et al., 2017; Barbieri et al., 1984; Einhorn et al., 1989; Merup et al., 1994; Pittman & Katovsky, 1984; Wawrzyniak et al., 2014), del(6)(q25) - 13 cases (Callet-Bauchu et al., 1999; Chena et al., 2003; Pedersen et al., 1994; Pittman & Katovsky, 1984; Sole et al., 1997; Travella et al., 2013).
The interstitial 6q- deletions included the following variants: del(6)(q12q26) - 2 cases (Einn et al., 1998; Huret et al., 1989), del(6)(q12q24) - 2 cases (Callet-Bauchu et al., 1996; Struski et al., 2007), del(6)(q13q15) - 4 cases (Baseggio et al., 2012; Travella et al., 2013; Wlodarska et al., 2007), del(6)(q13q21) -4 cases (Koduru et al., 1997; Morgan et al., 1999; Travella et al., 2013), del(6)(q13q23) - 4 cases (Li et al., 2016; Martin-Subero et al., 2007; Reddy et al., 2006), del(6)(q13q26) - 2 cases (Chapiro et al., 2008; Delhomme-Bachy et al., 1992), del(6)(q14q21) - 2 cases (Lopez et al., 2013; Odero et al., 2001), del(6)(q14q23) - 2 cases (Cuneo et al., 2004; Struski et al., 2007), del(6)(q15q21) - 3 cases (Asoa et al., 1994; Travella et al., 2013; Wawrzyniak et al., 2014), del(6)(q15q22) - 3 cases (Geisler et al., 1997; Put et al., 2009), del(6)(q15q23) - 5 cases (Geisler et al., 1997; Haferlach et al., 2007; Offit et al., 1994; Puiggros et al., 2014; Reddy et al., 2006), del(6)(q14q24) - 2 cases (Lopez et al., 2013; Van Den Neste et al., 2007), del(6)(q15q25) - 3 cases (Callet-Bauchu et al., 1999; Collado et al., 2017; Haferlach et al., 2007), del(6)(q15q22) - 5 cases (El-Taweel et al., 2009; Michaux et al., 1996; Pospisilova et al., 2007; Put et al., 2009; Van den Neste et al., 2007), del(6)(q21q23)- 9 cases (Autio et al., 1987; Cuneo et al., 2004; Geister et al., 1997; Lopes et al., 2012; Merup et al., 1998; Offit et al., 1994; Reddy, 2006; Iravella et al., 2013), del(6)(q21q24)- 2 cases (Brizard et al., 1997; Wren et al., 2010), del(6)(q21q25) - 9 cases (Collado et al., 2017; Delhomme-Bachy et al., 1992; Gardiner et al., 1997; Hamblin et al., 1999; Komatsu et al., 1993; Takashima et al., 1997; Wawrzyniak et al., 2014; Yin et al., 2009), del(6)(q23q25) - 4 cases (Cook et al., 2004; Peterson et al., 1992; Travella et al.,2013, Wong & Chan, 1999), del(6)(q21q27) - 2 cases (Offit et al., 1994), del(6)(q22q26) - 2 cases (Mehes et al., 2006).
In 44 cases (27%) the 6q- is present as sole anomaly, in 16 cases (9.8%) it is associated with one chromosome alteration and in 104 (63.4%) cases it is part of a complex karyotype. These data suggest that the 6q- could be primary, as well as secondary chromosome changes in the clonal evolution of CLL. In most of the cases the clones are hypodiploid, pseudodiploid or hyperdiploid. The most common additional numerical and structural anomalies are +12 (19 cases), +18 (10), -18 (7 cases observed only in cases with a terminal deletion), 13q- (16 cases), 11q- (18 cases) and 17p- (14 cases) and 14q32 rearrangements (21 cases, respectively t(14;18) in 4 cases, t(11;14) in 6 cases, t(8;14) in 3 cases and t(14;19) in 8 cases). The sex chromosomes are involved in chromosome aberrations in 9 cases.

Cytogenetics molecular

Fluorescent in situ hybridization, microarray comparative genome hybridization and exome-sequencing data Using probes mapping the bands 6q21and 6q27 Stilgenbauer S et al., 1999 found that the band 6q21 is deleted in all examined CLL cases with 6q-. Another study with probes mapping the bands 6q16, 6q23, 6q25 and 6q27 revealed that the most frequently deleted regions were at 6q16 and 6q25 (Dalsass et al., 2013). The examinations with array CGH carried out by Jarosova et al., 2017 found three types of 6q deletions: "large deletion" covering the entire 6q, "intermediate" deletion affecting the 6q telomeric region, but not the 6q12 centromeric region and "interstitial" deletions. The latter type deletions were heterogeneous and most of them covered the band 6q21. The authors mapped a minimal deleted region (MDR) (107.7-108.7 Mb) (5 cases) in the band 6q21 where are the genes SCML4, SEC63, OSTM1, NR2E1, SNX3, AFG1L (LACE1) and FOXO3 are located. Using array CGH Urbankova et al., 2014 described a similar MDR comprising a 1.4 Mb region at 6q21 (107.8-109.2 Mb) (2 cases) and Lehmann et al. a deletion of a small segment in 6q21 (107,003,343-107,132,119) (2 cases) in which only the gene CRYBG1 (AIM1) is located. Orgueira et al., 2019 presented exome-sequencing-based copy number aberration in the bands 6q15 (89479426-89563571) (1 case) and 6q21 (110797012-111583801) (1 case). The deleted segment in 6q15 (84kB) included only the gene RNGTT and the deleted segment in 6q21 (787Kb) the genes AMD1, CDK19, RPF2, GTFSC6, SLC16A10 and GSTM2P1.

Genes Involved and Proteins

Note
The existence of multiple 6q- variants that differ in length and localization indicates that the pathogenesis of the 6q- anomaly is complex and is associated with the involvement of different genes. However, it should be noted that pathogenetically the most significant band is 6q21, as it affects more than 70% of the 6q- cases with CLL. In this band an MDR coverage region of approximately 1.4 Kb is reported by two different scientific teams. Jarosova M et al., 2017 demonstrated that of the genes that are localized in the noted region (see above), the genes FOXO3, LACE1, SNX3 and SCML4 have low mRNA expression in CLL cases with 6q- compared to those without the deletion and healthy controls. The authors hypothesized that FOXO3 is the candidate tumor suppressor gene located at the 6q21 region based on its low mRNA expression level, as well as that the reduced pro-apoptotic function of this gene could lead to aberrant overactivation of the phosphoinositol-3-kinase/protein kinase B (PI3K/AKt) cascade and prolonged cell survival (Zhang X et al., 2011). FOXO3 belongs to the forkhead transcription factors that in mammals include also the members FOXO1, FOXO4 and FOXO6 and are characterized by a winged-helix DNA binding motif and forkhead domain (Obsil T & Obsilova V, 2008). Its deregulation has been implicated in different pathological conditions as cardiovascular and neurological diseases, muscle atrophy, premature ovarian failure and tumorigenesis. It is accepted that FOXO3 acts as a tumor suppressor gene in many solid tumors including colon, liver, prostate, bladder and breast cancer. FOXO3 is involved also in numerous cellular processes, such as apoptosis, proliferation, cell cycle progression, DNA damage response and longevity. Considering the important role of FOXO3 in the regulation of DNA damage signaling pathway and that CLL is a disease in which the most common chromosomal abnormalities 13q-, 11q-, +12/12q+ and 17p- affect genes associated with the same pathway, such as MIR-15/16, ATM, MDM2 and TP53, further suggest that FOXO3 could be a major player in the molecular pathogenesis of CLL in the cases with 6q21 deletion. The fact that the ATM and TP53 are downstream targets of FOXO3 and it forms a complex with them to trigger apoptosis upon DNA damage (Chung YM et al, 2012) confirms this assumption. However, in about 30% of cases the band 6q21 is not affected, indicating that besides FOXO3, other genes are also associated with the pathogenesis of 6q- anomaly. Interestingly, in all interstitial 6q- deletions distal from 6q21 and in all terminal 6q- deletions the band 6q25 is involved. In this chromosomal band is located the gene of SOD2 (manganese superoxide dismutase) (6q25.3) that also plays a very important role for cell protection against DNA damage removing superoxide radicals. SOD2 is 23kDa homotetramer - mitochondrial enzyme that dismutates superoxide to hydrogen peroxide. Its transcription is directly stimulated by FOXO3. Deficiencies of SOD2 caused by deletion of 6q25 or mutation of the SOD2 gene are associated with several types of cancer (Oberley et al., 1979; Xu et al; 1999). On the other hand it has been reported that SOD2 reduces tumor development and metastatic ability (Church et al., 1993; Urano et al., 1995; Zhong et al., 1997; Liu et al., 2009). Therefore it has been accepted that SOD2 may act as a tumor suppressor protecting cells from oxidant - induced cancerogenesis. SOD2 is at the bifurcation point between both one-electron (superoxide mediated) and two-electron (hydrogen peroxide mediated) signaling pathways and its activity modulates the levels of both intracellular messengers superoxide anions and hydrogen peroxide. The hydrogen peroxide mediated pathway include the oxidation of phosphatase and tensin homologs deleted on chromosome 10 ( PTEN) by the hydrogen peroxide leading to suppression of its phosphatase activity by formation of a disulfide bond between cysteine residues Cys124 and Cys71 (Lee CU et al., 2015). In a physiological condition this mechanism is responsible for the activation of the PI3K/Act signaling. Oxidized PTEN can be reversibly converted back to its reduced form by the cellular-reducing systems, such as thioredoxin ( TXN) and glutaredoxin ( GLRX) (Lee SR, et al 2002; Schwertassek U et al., 2014), which in turn activates PTEN and subsequently inhibits the PI3K/Act mediated signaling. It is known that the loss of SOD2 results in increased levels of superoxide anion and respectively in enhanced oxidative damage such as membrane lipid peroxidation, protein carbonylation and DNA damage (Elchuri et al., 2005; Yang et al., 2007). It is logical to suppose that the generated by superoxide anion secondary radical species such as OH-, NO2- and CO32- could be relevant for the promotion of B-CLL with 6q25 deletion. These radicals may cause irreversible redox-sensitive inactivation of PTEN by impairing the cellular-reducing systems TXN and GLRX, which will lead to uncontrolled pro-survival signaling of the PI3K/Act pathway.
The data presented above suggest that the deletion of the genes FOXO3 and/or SOD2 in CLL may promote deregulation of DNA damage signaling leading to prolonged cell survival instead of DNA repair or apoptosis.

Bibliography

Pubmed IDLast YearTitleAuthors
294834962017Comparison of chromosomal rearrangements in bone marrow cells and blast transformed B-cells in relapse of B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma.Andreieva SV et al
81362711993Japanese B cell chronic lymphocytic leukaemia: a cytogenetic and molecular biological study.Asou H et al
36917551987Cytogenetic and immunologic characterization of mitotic cells in chronic lymphocytic leukaemia.Autio K et al
64326401984Cytogenetic evaluation of bone marrow involvement in non-Hodgkin's lymphomas. A survey of 94 cases.Barbieri D et al
226861902012In non-follicular lymphoproliferative disorders, IGH/BCL2-fusion is not restricted to chronic lymphocytic leukaemia.Baseggio L et al
247780362014Genetics of lymphocytes influences the emergence of second cancer in chronic lymphocytic leukemia.Bernués M et al
68506081983Nonrandom chromosome abnormalities in lymphoma.Bloomfield CD et al
242466922014Clonal evolution in chronic lymphocytic leukemia detected by fluorescence in situ hybridization and conventional cytogenetics after stimulation with CpG oligonucleotides and interleukin-2: a prospective analysis.Brejcha M et al
9250825199711q13 rearrangement in B cell chronic lymphocytic leukemia.Brizard F et al
89461981996dic(4;17)(p11;p11): a new recurrent chromosomal abnormality in chronic B-lymphoid disorders.Callet-Bauchu E et al
226960502012Cytogenetic and molecular cytogenetic profile of bone marrow-derived mesenchymal stromal cells in chronic and acute lymphoproliferative disorders.Campioni D et al
184492072008The most frequent t(14;19)(q32;q13)-positive B-cell malignancy corresponds to an aggressive subgroup of atypical chronic lymphocytic leukemia.Chapiro E et al
145539502003Interphase cytogenetic analysis in Argentinean B-cell chronic lymphocytic leukemia patients: association of trisomy 12 and del(13q14).Chena C et al
228931242012FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage.Chung YM et al
84649311993Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells.Church SL et al
86082421996Detection of 11q13 rearrangements in hematologic neoplasias by double-color fluorescence in situ hybridization.Coignet LJ et al
288889942017Chronic lymphocytic leukemia with isochromosome 17q: An aggressive subgroup associated with TP53 mutations and complex karyotypes.Collado R et al
151983542004Utility of routine classical cytogenetic studies in the evaluation of suspected lymphomas: results of 279 consecutive lymph node/extranodal tissue biopsies.Cook JR et al
30383001987Chromosome abnormalities in chronic lymphocytic leukemia revealed by cytochalasin B and Epstein-Barr virus.Crossen PE et al
118014642002Late appearance of the 11q22.3-23.1 deletion involving the ATM locus in B-cell chronic lymphocytic leukemia and related disorders. Clinico-biological significance.Cuneo A et al
147122872004Chronic lymphocytic leukemia with 6q- shows distinct hematological features and intermediate prognosis.Cuneo A et al
2356044120136q deletion detected by fluorescence in situ hybridization using bacterial artificial chromosome in chronic lymphocytic leukemia.Dalsass A et al
15020241992Chromosome studies in stimulated lymphocytes of 50 patients with B-cell chronic lymphocytic leukemia.Delhomme-Bachy M et al
168407332006Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: A study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression.Dicker F et al
25861801989Molecular analyses of chromosome 12 in chronic lymphocytic leukemia.Einhorn S et al
198372672009Detection of chromosomal abnormalities associated with chronic lymphocytic leukemia: what is the best method?El-Taweel M et al
155319192005CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life.Elchuri S et al
8280621976Natural antibodies and immune antibodies of human ABO blood group system.Filitti-Wurmser S et al
97986601998Secondary abnormalities of chromosome 6q in B-cell chronic lymphocytic leukemia: a sequential study of karyotypic instability in 51 patients.Finn WG et al
27376671989Chromosomal characteristics of malignant lymphoma.Fleischman EW et al
92909571997Cytogenetic, fluorescence in situ hybridisation, and clinical evaluation of translocations with concomitant deletion at 13q14 in chronic lymphocytic leukaemia.Gardiner AC et al
94449331997In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: a cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients.Geisler CH et al
289242432018Refined karyotype-based prognostic stratification of chronic lymphocytic leukemia with a low- and very-low-risk genetic profile.Giudice ID et al
178053272007Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping.Haferlach C et al
104777131999Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia.Hamblin TJ et al
90782991997del(7q) in chronic B-cell lymphoid malignancies.Hernandez JM et al
171292292007The t(14;19)(q32;q13)-positive small B-cell leukaemia: a clinicopathologic and cytogenetic study of seven cases.Huh YO et al
215024232011Chronic lymphocytic leukemia with t(14;19)(q32;q13) is characterized by atypical morphologic and immunophenotypic features and distinctive genetic features.Huh YO et al
28177761989Karyotypes of 33 patients with clonal aberrations in chronic lymphocytic leukaemia. Review of 216 abnormal karyotypes in chronic lymphocytic leukaemia.Huret JL et al
286991852017Chromosome 6q deletion correlates with poor prognosis and low relative expression of FOXO3 in chronic lymphocytic leukemia patients.Jarosova M et al
38711611985Prognostic information from cytogenetic analysis in chronic B-lymphocytic leukemia and leukemic immunocytoma.Juliusson G et al
206206032010Deletion of 5q as a rare abnormality in chronic lymphocytic leukemia.Karakosta M et al
93546781997Correlation between mutation in P53, p53 expression, cytogenetics, histologic type, and survival in patients with B-cell non-Hodgkin's lymphoma.Koduru PR et al
238935752013Clonal evolution in chronic lymphocytic leukemia: analysis of correlations with IGHV mutational status, NOTCH1 mutations and clinical significance.López C et al
24012721990Inhalation pharmacokinetics of 1,3-butadiene and 1,2-epoxybutene-3 in rats and mice.Laib RJ et al
264185322015Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and Bisperoxidovanadium Complexes.Lee CU et al
119169652002Reversible inactivation of the tumor suppressor PTEN by H2O2.Lee SR et al
182465372008Molecular allelokaryotyping of early-stage, untreated chronic lymphocytic leukemia.Lehmann S et al
28363211988Direct outgrowth of in vivo Epstein-Barr virus (EBV)-infected chronic lymphocytic leukemia (CLL) cells into permanent lines.Lewin N et al
220025752012B-cell lymphomas with MYC/8q24 rearrangements and IGH@BCL2/t(14;18)(q32;q21): an aggressive disease with heterogeneous histology, germinal center B-cell immunophenotype and poor outcome.Li S et al
269160702016The clinical significance of 8q24/MYC rearrangement in chronic lymphocytic leukemia.Li Y et al
193844242009Protandim, a fundamentally new antioxidant approach in chemoprevention using mouse two-stage skin carcinogenesis as a model.Liu J et al
199631362010Genetic and immunophenotypic profile of IGH@ rearrangement detected by fluorescence in situ hybridization in 149 cases of B-cell chronic lymphocytic leukemia.Lu G et al
169634002006Karyotype complexity and VH gene status in B-cell chronic lymphocytic leukemia.Méhes G et al
174959772007A comprehensive genetic and histopathologic analysis identifies two subgroups of B-cell malignancies carrying a t(14;19)(q32;q13) or variant BCL3-translocation.Martín-Subero JI et al
161793742006Chromosomal translocations are associated with poor prognosis in chronic lymphocytic leukemia.Mayr C et al
95932681998A FISH cosmid 'cocktail' for detection of 13q deletions in chronic lymphocytic leukaemia--comparison with cytogenetics and Southern hybridization.Merup M et al
81990171994T-cell receptor beta gene rearrangements in leukaemic B-cells from patients with chronic lymphocytic leukaemia: association with chromosome 6 deletions.Merup M et al
88247241996BCL3 rearrangement and t(14;19)(q32;q13) in lymphoproliferative disorders.Michaux L et al
100879471999PHA/IL2: an efficient mitogen cocktail for cytogenetic studies of non-Hodgkin lymphoma and chronic lymphocytic leukemia.Morgan R et al
316164672019New Recurrent Structural Aberrations in the Genome of Chronic Lymphocytic Leukemia Based on Exome-Sequencing Data.Mosquera Orgueira A et al
32601261988Karyotypic stability in chronic B-cell leukemia.Nowell PC et al
2175311979Role of superoxide dismutase in cancer: a review.Oberley LW et al
183919692008Structure/function relationships underlying regulation of FOXO transcription factors.Obsil T et al
116727672001Comparative genomic hybridization and amplotyping by arbitrarily primed PCR in stage A B-CLL.Odero MD et al
81673421994Clinical and morphologic features of B-cell small lymphocytic lymphoma with del(6)(q21q23).Offit K et al
2155959219946q(-) as the only cytogenetic aberration - loss of 6q23 and survival in hematologic malignancies.Pedersen B et al
13779331992Frequent clonal abnormalities of chromosome band 13q14 in B-cell chronic lymphocytic leukemia: multiple clones, subclones, and nonclonal alterations in 82 midwestern patients.Peterson LC et al
63350481984Prognostic significance of chromosome abnormalities in chronic lymphocytic leukaemia.Pittman S et al
175257292007Interstitial del(14)(q) involving IGH: a novel recurrent aberration in B-NHL.Pospisilova H et al
249157572014Interstitial 13q14 deletions detected in the karyotype and translocations with concomitant deletion at 13q14 in chronic lymphocytic leukemia: different genetic mechanisms but equivalent poorer clinical outcome.Puiggros A et al
192955472009Translocation t(14;18) is not associated with inferior outcome in chronic lymphocytic leukemia.Put N et al
164871712006Chronic lymphocytic leukaemia profiled for prognosis using a fluorescence in situ hybridisation panel.Reddy KS et al
170745922006Genetic abnormalities and clinical outcome in chronic lymphocytic leukemia.Ripollés L et al
38020501987Clonal chromosome abnormalities in chronic lymphocytic leukemia patients revealed by TPA stimulation of whole blood cultures.Ross FM et al
157162442005Expression of bcl-3 in chronic lymphocytic leukemia correlates with trisomy 12 and abnormalities of chromosome 19.Schlette E et al
249761392014Reactivation of oxidized PTP1B and PTEN by thioredoxin 1.Schwertassek U et al
90783021997Cytogenetic studies in seventy-six cases of B-chronic lymphoproliferative disorders.Solé F et al
32973041987Chromosomal abnormalities in indolent lymphoma.Speaks SL et al
104829821999Incidence and clinical significance of 6q deletions in B cell chronic lymphocytic leukemia.Stilgenbauer S et al
166902282007[A cytological, immunophenotypical and cytogenetical study of 136 consecutive cases of B-cell chronic lymphoid hemopathies].Struski S et al
92122191997Detection of 14q32.33 translocation and t(11;14) in interphase nuclei of chronic B-cell leukemia/lymphomas by in situ hybridization.Takashima T et al
229619732013Structural alterations in chronic lymphocytic leukaemia. Cytogenetic and FISH analysis.Travella A et al
179255622007Assessment of chronic lymphocytic leukemia and small lymphocytic lymphoma by absolute lymphocyte counts in 2,126 patients: 20 years of experience at the University of Texas M.D. Anderson Cancer Center.Tsimberidou AM et al
77809531995Expression of manganese superoxide dismutase reduces tumor control radiation dose: gene-radiotherapy.Urano M et al
230735272014Array-based karyotyping in chronic lymphocytic leukemia (CLL) detects new unbalanced abnormalities that escape conventional cytogenetics and CLL FISH panel.Urbankova H et al
175413982007Chromosomal translocations independently predict treatment failure, treatment-free survival and overall survival in B-cell chronic lymphocytic leukemia patients treated with cladribine.Van Den Neste E et al
268500072016Genomic alterations of the JAK2 and PDL loci occur in a broad spectrum of lymphoid malignancies.Van Roosbroeck K et al
16430181992Chromosome 11q rearrangements in B non Hodgkin's lymphoma.Vandenberghe E et al
241385502014Clonal evolution in CLL patients as detected by FISH versus chromosome banding analysis, and its clinical significance.Wawrzyniak E et al
172513352007Telomeric IGH losses detectable by fluorescence in situ hybridization in chronic lymphocytic leukemia reflect somatic VH recombination events.Wlodarska I et al
86839741996Trisomy 12 is a rare cytogenetic finding in typical chronic lymphocytic leukemia.Woessner S et al
103265921999Cytogenetic abnormalities in chronic B-cell lymphoproliferative disorders in Chinese patients.Wong KF et al
203622312010Cytogenetic investigations of chronic lymphocytic leukemia.Wren C et al
99269241999Mutations in the promoter reveal a cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells.Xu Y et al
180734242007A Measurable increase in oxidative damage due to reduction in superoxide detoxification fails to shorten the life span of long-lived mitochondrial mutants of Caenorhabditis elegans.Yang W et al
193696252009Chronic lymphocytic leukemia With t(2;14)(p16;q32) involves the BCL11A and IgH genes and is associated with atypical morphologic features and unmutated IgVH genes.Yin CC et al
64671791984Recurrent chromosomal defects are found in most patients with non-Hodgkin's-lymphoma.Yunis JJ et al
106268231999Comparison of effects of two polymorphic variants of manganese superoxide dismutase on human breast MCF-7 cancer cell phenotype.Zhang HJ et al
214400112011Akt, FoxO and regulation of apoptosis.Zhang X et al
90538451997Suppression of the malignant phenotype of human glioma cells by overexpression of manganese superoxide dismutase.Zhong W et al

Citation

Liliya Grahlyova ; Lubomir Mitev

Del(6q) in Chronic lymphocytic leukaemia (CLL)

Atlas Genet Cytogenet Oncol Haematol. 2020-01-01

Online version: http://atlasgeneticsoncology.org/haematological/2011/del(6q)-in-chronic-lymphocytic-leukaemia-(cll)

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