del(6q) abnormalities in lymphoid malignancies
1998-12-01 Chrystele Bilhou-Nabera , Christophe Brigaudeau Affiliation1.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 ID | Last Year | Title | Authors |
|---|---|---|---|
| 8605327 | 1996 | Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A Collaborative Study of the Group Français de Cytogénétique Hématologique. | |
| 9369429 | 1997 | Chromosome aberrations in atypical chronic lymphocytic leukemia: a cytogenetic and interphase cytogenetic study. | Bigoni R et al |
| 8751467 | 1996 | A low rate of loss of heterozygosity is found at many different loci in childhood B-lineage acute lymphocytic leukemia. | Cavé H et al |
| 9009085 | 1997 | Delineation of a 6 cM commonly deleted region in childhood acute lymphoblastic leukemia on the 6q chromosomal arm. | Gérard B et al |
| 2207332 | 1990 | Abnormalities of the long arm of chromosome 6 in childhood acute lymphoblastic leukemia. | Hayashi Y et al |
| 9552025 | 1998 | Frequency 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 |
| 9558398 | 1998 | 6q deletions in acute lymphoblastic leukemia and non-Hodgkin's lymphomas. | Merup M et al |
| 8167342 | 1994 | Clinical and morphologic features of B-cell small lymphocytic lymphoma with del(6)(q21q23). | Offit K et al |
| 9054669 | 1997 | Cytogenetics 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 |
| 9635588 | 1998 | Frequent 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.
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/del(6q)-abnormalities-in-lymphoid-malignancies
