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Unusual deletions within the immunoglobulin heavy-chain locus in acute
leukemias
MJ Dyer, JM Heward, VJ Zani, V Buccheri and D Catovsky
Academic Department of Haematology and Cytogenetics, Institute of Cancer
Research-Royal Marsden Hospital, Haddow Laboratories, Sutton, Surrey, UK.
We have investigated the structure of the Ig heavy (IGH) chain locus in 309
cases of acute leukemia. Seventy-one cases of B-cell precursor (BCP) acute
lymphoblastic leukemia (ALL) were analyzed: in six cases deletion of
joining (JH) segments in the presence of cytogenetically normal chromosome
14 was observed. Similar deletions were seen in 1 out of 8 cases of
biphenotypic acute leukemia analyzed: this case exhibited t(9:22)(q34;q11)
and coexpressed both myeloid and B cell differentiation antigens. Five of
the 7 cases analyzed had deleted the JH segments from both chromosomes.
Because these deletions may have contributed to the pathogenesis of the
disease we have attempted to define their boundaries. Using probes that map
both 5' and 3' of JH, the 3' (centromeric) boundary of the deletions was
mapped to an approximately 30-kb central region of the 60 kb between C
delta and C gamma 3 in 10 of the 12 deleted chromosomes. In the remaining
two chromosomes, the 3' boundary mapped to S mu. The 5' (telomeric)
boundary could not be defined. However, three cases with biallelic deletion
of JH showed biallelic deletion of the most proximal variable (VH) (VH6 and
VH5-B2) genes, indicating that the deletions spanned over 500 kb. VH5-B1
and VH5-B3 were retained in germline configuration and no gross deletions
were observed using a VH3 subgroup-specific probe, indicating that the 5'
boundary mapped within the VH locus. Unusual deletions of the portion of
the IgH locus including JH segments and the C mu and C delta genes may
occur in acute leukemias with immunophenotypic evidence of commitment to
the B cell differentiation pathway. The possible consequences of the
deletions remain to be determined. However, the clustering of the
centromeric boundary of the deletions to S mu and to a region between the C
delta-C gamma 3 genes, a known "hot spot" for recombination, may indicate
the operation of a distinct pathogenic mechanism.
Volume 82,
Issue 3,
pp. 865-871,
08/01/1993
Copyright © 1993 by The American Society of Hematology
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