del(6q) abnormalities in lymphoid malignancies

1998-12-01   Chrystele Bilhou-Nabera  , Christophe Brigaudeau  

1.Laboratoire d Hématologie, Hôpital du Haut-Lévêque, CHU de Bordeaux, Ave de Magellan, 33 604 Pessac, France
2.Laboratoire dHématologie, Hôpital du Haut-Lévêque, CHU de Bordeaux, Ave de Magellan, 33 604 Pessac, France

Clinics and Pathology

Disease

childhood B-cell acute lymphoblastic leukemia (B-ALL)

Phenotype stem cell origin

lack of specificity for a particular immunophenotype

Epidemiology

found in 5-15% of patients after conventional cytogenetic analysis, in 30% after FISH analysis, in 5 to 25% of cases in loss of heterozygosity studies.

Prognosis

not significantly different from patients lacking a 6q rearrangement

Disease

atypical chronic lymphocytic leukemia

Epidemiology

del(6q) is one of the most frequent cytogenetic aberration occurring in 10-20% of cases and often associated with 14q11 or del(9p) abnormalities.

Prognosis

outcome similar to cases with normal diploid karyotypes

Disease

adult acute lymphoblastic leukemia

Phenotype stem cell origin

T-cell phenotype found in 50% of cases (ALL)

Epidemiology

del(6q) in adult-ALL occur with a lower frequency (5%) than in children and is reported predominantly in young adult (15 to 40 years aged).

Prognosis

patients with a 6q change tented to have longer event free survival (EFS) (median: 11 months; 3 years EFS: 47%) than did patients without 6q changes (median EFS: 7 month; 3 years EFS: 20%).

Disease

B-cell small lymphocytic lymphomA

Epidemiology

del(6)(q21q23) is the most common recurrent cytogenetic abnormality in this disease

Clinics

in cases with del(6q), a morphological appearance of peripheral blood large prolymphocytes, a mature B-cell phenotype and a typical clinical course of other well-differentiated lymphocytic neoplams are described

Prognosis

complex karyotypes with +12, del(13)(q14), del(11q), del(6)(q21q23) and possible 4q or 10q anomalies are associated with a poor prognosis.

Disease

multiple myeloma

Phenotype stem cell origin

multiple myeloma (MM) is a malignant plasma cell proliferation of mature differentiated B-cell.

Epidemiology

del (6q) in multiple myeloma represent 15% of cases of MM

Prognosis

del(6q) are more frequent in the hypodiploid group of multiple myeloma, bearing a worse prognosis (med survival of 1.5 yr).

Genes Involved and Proteins

Note
6q21 band loss suggests the presence of a recessive tumour suppressor gene whose absence might contribute to malignant transformation and development of both T and precursor B-ALLs; the lack of specificity for a particular immunophenotype may imply that the gene or genes affected by 6q abnormalities are broadly active in the multistep process of lymphoid leukemogenesis.

Putative tumour suppressor gene(s) on chromosome arm 6q remains to be identified; to demonstrate this loss of heterozygosity of informative markers (LOH) was analysed using PCR amplification of polymorphic microsatellite sequences; using polymorphic markers located from the 6q14-15 to telomere, LOH was detected in 5 to 25% of childhood ALL cases.

Regarding LOH results, two distinct regions were identified:- first region flanked by D6S283 and D6S302 loci at 6q21-22- second region flanked by D6S275 and D6S283 loci at 6q21

Using LOH analysis on several cases, the authors demonstrated an identical 6q21-22 structure at diagnosis and at relapse, suggesting that 6q deletion may be an initial event in leukemogenesis and may occur less frequently during progression of the disease.

Article Bibliography

Pubmed IDLast YearTitleAuthors
86053271996Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A Collaborative Study of the Group Français de Cytogénétique Hématologique.
93694291997Chromosome aberrations in atypical chronic lymphocytic leukemia: a cytogenetic and interphase cytogenetic study.Bigoni R et al
87514671996A low rate of loss of heterozygosity is found at many different loci in childhood B-lineage acute lymphocytic leukemia.Cavé H et al
90090851997Delineation of a 6 cM commonly deleted region in childhood acute lymphoblastic leukemia on the 6q chromosomal arm.Gérard B et al
22073321990Abnormalities of the long arm of chromosome 6 in childhood acute lymphoblastic leukemia.Hayashi Y et al
95520251998Frequency and clinical significance of cytogenetic abnormalities in pediatric T-lineage acute lymphoblastic leukemia: a report from the Children's Cancer Group.Heerema NA et al
955839819986q deletions in acute lymphoblastic leukemia and non-Hodgkin's lymphomas.Merup M et al
81673421994Clinical and morphologic features of B-cell small lymphocytic lymphoma with del(6)(q21q23).Offit K et al
90546691997Cytogenetics adds independent prognostic information in adults with acute lymphoblastic leukaemia on MRC trial UKALL XA. MRC Adult Leukaemia Working Party.Secker-Walker LM et al
96355881998Frequent loss of heterozygosity on the long arm of chromosome 6: identification of two distinct regions of deletion in childhood acute lymphoblastic leukemia.Takeuchi S et al

Summary

Note

deletion of the long arm of chromosome 6 (del(6q)) is more frequently described in lymphoid proliferations than in other hematological malignancies; del(6q) is observed in acute lymphoblastic leukemia (ALL), in chronic lymphocytic leukemia (CLL), in prolymphocytic leukemia and in non-Hodgkin lymphomas (NHL) (15% cases, sometimes associated with t(14;18)(q32;q21)); these deletions are mainly reported to be terminal, but also interstitial.
Atlas Image
del(6q)  Partial karyotypes with 6q deletions of various sizes (6 left u2013 Courtesy Adriana Zamecnikova; 2 center right: Courtesy Diane H. Norback, Eric B. Johnson, Sara Morrison-Delap Cytogenetics at theWaisman Center; right: R- banding u2013 Jean Loup Huret. Hybridization with the XL 6q21/6q23 locus-specific probe (Metasystems, Germany) showing the green labeled probe hybridizing to 6q21 and the orange labeled probe hybridizing to the MYB gene region at 6q23 on normal metaphase (A) and on metaphase with 6q deletion distal to 6q23 (B). Two green and one orange signal indicate a deletion in 6q23 (MYB) (C) u2013 Courtesy Adriana Zamecnikova.

Citation

Chrystele Bilhou-Nabera ; Christophe Brigaudeau

del(6q) abnormalities in lymphoid malignancies

Atlas Genet Cytogenet Oncol Haematol. 1998-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1148/haematological-explorer/css/lib/deep-insight-explorer/