Aberrant rearrangements within the immunoglobulin heavy chain locus in hairy cell leukemia.
The cell surface expression of multiple immunoglobulin heavy chain (IGH) isotypes, preferentially observed in hairy cell leukemia (HCL), is incompatible with the deletion model of IGH class switching, and alternative models involving RNA-splicing have been proposed. To help discriminate between these possibilities we have examined the configuration of the IGH locus by DNA blot in 38 cases of HCL. Deletion of at least one allele of C mu/C delta was seen in 14 cases (37%). Of 12 cases in which IgG and/or IgA were expressed, three exhibited biallelic deletion of C mu/C delta compatible with deletional class-switching whereas the remaining 9 cases retained both alleles of C mu/C delta. These data indicate that both DNA deletion and RNA-splicing mechanisms of class-switching may operate in HCL. In a further 17 cases, other unexpected abnormalities of the IGH locus mapping to the JH-C mu intron in one of two patterns were observed. First, discordance between JH and C mu in BamHI DNA digests was found in 12 cases. Similar patterns were observed in only 4/91 cases of B-cell chronic lymphocytic leukemia and 0/15 of B-cell prolymphocytic leukemia. To preclude chromosomal translocations involving the JH-C mu intron, rearrangements of BCL1, BCL2, BCL3, and MYC were sought in 23 cases but none of the cases showed oncogene rearrangement to the intron. Second, abnormal-sized C mu fragments arising as a consequence of abnormalities of the JH-C mu intron were detected in HindIII, BgIII, and/or Xbal digests in 10/23 cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Kayano
H
H
Academic Department of Haematology and Cytogenetics, Haddow Laboratories, Institute of Cancer Research, Sutton, UK.
Dyer
M J
MJ
Zani
V J
VJ
Laffan
M A
MA
Matutes
E
E
Asou
N
N
Katayama
I
I
Catovsky
D
D
D000483:Alleles; D004273:DNA, Neoplasm / Q000235:genetics; D017353:Gene Deletion; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D015151:Immunoblotting; D007070:Immunoglobulin A / Q000235:genetics; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007128:Immunoglobulin Fragments / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007132:Immunoglobulin Isotypes / Q000235:genetics; D007134:Immunoglobulin Switch Region / Q000235:genetics; D016130:Immunophenotyping; D007438:Introns; D007943:Leukemia, Hairy Cell / Q000235:genetics*; D012326:RNA Splicing
D004273:DNA, Neoplasm; D007070:Immunoglobulin A; D007127:Immunoglobulin Constant Regions; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes