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Título:
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Utilization of Ig heavy chain variable, diversity, and joining gene segments in children with B-lineage acute lymphoblastic leukemia: implications for the mechanisms of VDJ recombination and for pathogenesis
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Autor/a:
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Li, Aihong; Rué i Monné, Montserrat; Zhou, Jianbiao; Wang, Hongjun; Goldwasser, Meredith A.; Neuberg, Donna; Dalton, Virginia; Zuckerman, David; Lyons, Cheryl; Silverman, Lewis B.; Sallan, Stephen E.; Gribben, John G.
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Notas:
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Sequence analysis of the immunoglobulin
heavy chain genes (IgH) has demonstrated
preferential usage of specific variable
(V), diversity (D), and joining (J)
genes at different stages of B-cell development
and in B-cell malignancies, and
this has provided insight into B-cell maturation
and selection. Knowledge of the
association between rearrangement patterns
based on updated databases and
clinical characteristics of pediatric acute
lymphoblastic leukemia (ALL) is limited.
We analyzed 381 IgH sequences identi-
fied at presentation in 317 children with
B-lineage ALL and assessed the VHDHJH
gene utilization profiles. The DHJH-proximal
VH segments and the DH2 gene family
were significantly overrepresented. Only
21% of VH-JH joinings were potentially
productive, a finding associated with a
trend toward an increased risk of relapse.
These results suggest that physical location
at the VH locus is involved in preferential
usage of DHJH-proximal VH segments
whereas DH and JH segment usage is
governed by position-independent molecular
mechanisms. Molecular pathophysiology
appears relevant to clinical
outcome in patients who have only productive
rearrangements, and specific rearrangement
patterns are associated with
differences in the tumor biology of childhood
ALL. |
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Derechos:
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(c) The American Society of Hematology, 2004
info:eu-repo/semantics/restrictedAccess |
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Tipo de documento:
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article
publishedVersion |
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Editor:
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American Society of Hematology
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