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Blood, 1 May 2001, Vol. 97, No. 9, pp. 2716-2726
IMMUNOBIOLOGY
Immunoglobulin heavy-chain gene rearrangement in adult acute
lymphoblastic leukemia reveals preferential usage of
JH-proximal variable gene segments
Forida Y. Mortuza,
Ilidia
M. Moreira,
Maria Papaioannou,
Paula Gameiro,
Luke A. Coyle,
Clair S. Gricks,
Peter Amlot,
Hugh Grant Prentice,
Alejandro Madrigal,
Alan Victor Hoffbrand, and
Letizia Foroni
From the Department of Haematology and Immunology,
Royal Free and University College of London (Royal Free Campus),
London, United Kingdom.
The aim of this study was to characterize individual-segment and
overall patterns of VH gene usage in adult
B-lineage acute lymphoblastic leukemia (ALL). Theoretical values of
VH segment usage were calculated with the assumption that
all VH segments capable of undergoing
rearrangement have an equal probability of selection for
recombination. Leukemic clones from 127 patients with adult B-lineage
acute leukemias were studied by fingerprinting by means of primers for
the framework 1 and joining segments. Clones from early
preimmune B cells (245 alleles identified) show a predominance
of VH6 family rearrangements and, consequently, do not
conform to this hypothesis. However, profiles of VH gene family usage in mature B cells, as investigated in peripheral blood (6 samples), B-cell lymphomas (36 clones) and chronic lymphocytic leukemia
(56 clones), are in agreement with this theoretical profile. Sequence
analyses of 64 VH clones in adult ALL revealed that the rate of VH usage is proportional to the proximity of the
VH gene to the JH locus and that the
relationship can be mathematically defined. Except for VH6,
no other VH gene is excessively used in adult ALL.
VH pseudogenes are rarely used (n = 2), which
implies the existence of early mechanisms in the pathway to B-cell
maturation to reduce wasteful
VH-(DH)-JH
recombination. Finally, similar to early immunoglobulin-H
rearrangement patterns in the mouse, B cells of ALL derive from a pool
of cells more immature than the cells in chronic lymphoid B-cell malignancies.
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