Abnormalities of the long arm of chromosome 6 in childhood acute lymphoblastic leukemia
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Y Hayashi1, S C Raimondi, A T Look
1Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38101.
Insights
Structural rearrangements of chromosome 6 long arm (6q) in acute lymphoblastic leukemia (ALL) are linked to specific genetic alterations. These 6q abnormalities may indicate a tumor suppressor gene locus, impacting leukemogenesis.
Area of Science:
- Cytogenetics
- Pediatric Oncology
- Molecular Biology
Background:
- Structural rearrangements of the long arm of chromosome 6 (6q) are observed in acute lymphoblastic leukemia (ALL).
- The biologic significance of these 6q abnormalities at diagnosis requires further investigation.
Purpose of the Study:
- To determine the biologic significance of 6q structural rearrangements in pediatric ALL.
- To investigate the association between 6q abnormalities and immunophenotype, clinical features, and survival.
Main Methods:
- Karyotypic analysis of leukemic cells from 412 children with ALL.
- Classification of 6q abnormalities into deletions and translocations.
- Correlation of 6q abnormalities with immunophenotype and clinical outcomes.
Main Results:
- Eleven percent (45/412) of children with ALL had 6q abnormalities.
- Deletions encompassing the 6q21 band were common, suggesting a potential tumor suppressor gene locus.
- A novel nonrandom translocation t(6;12)(q21;p13) was identified in two cases with early pre-B ALL.
- Children with 6q abnormalities were less likely to have a pre-B immunophenotype but survival was similar.
Conclusions:
- 6q abnormalities in ALL may involve a recessive tumor suppressor gene at 6q21.
- The gene(s) affected by 6q abnormalities are likely broadly active in lymphoid leukemogenesis.
- Molecular studies are needed to identify submicroscopic deletions and further elucidate the role of 6q abnormalities in ALL.
Abstract:
To determine the biologic significance of the structural rearrangements of the long arm of chromosome 6(6q) in acute lymphoblastic leukemia (ALL) at diagnosis, we studied 412 consecutive children whose leukemic cell chromosomes had been completely banded and identified 45 (11%) children with this abnormality. The 45 cases were divided into del(6q) only (n = 11), del(6q) and numerical abnormalities (n = 4), del(6q) and structural abnormalities (n = 23), and 6q translocations (n = 7). The breakpoints of del(6q) were subgrouped: del(6)(q15q21) in 11 cases, del(6) (q13q21) in six, del(6)(q21q23) in four, del(6)(q15) in four, del(6)(q15q23) in three, and other deletions in 10 cases. Notably, all these deletions encompassed the 6q21 band, suggesting that this might be the locus of a recessive tumor suppressor gene, the absence of which contributes to malignant transformation or proliferation. Among the seven children with 6q translocations, a previously unidentified nonrandom translocation, t(6;12)(q21;p13) was noted in two cases with an early pre-B immunophenotype. Clinical features and event-free survival were similar among children with or without 6q abnormalities. Overall, children with 6q abnormalities were less likely than those without the abnormality to have a pre-B immunophenotype (P = .03). T-cell immunophenotypes were equally represented in cases with or without 6q abnormalities. However, all four children with del(6q) and a 12p abnormality had early pre-B ALL and all three children with del(6q) and a 9p abnormality had a T-cell immunophenotype. 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. The relatively high frequency of microscopically visible del(6q) indicates the need for molecular studies to identify cases with submicroscopic deletions.