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Biologic and prognostic significance of the presence of more than two mu
heavy-chain genes in childhood acute lymphoblastic leukemia of B precursor
cell origin
GR Kitchingman, J Mirro, S Stass, U Rovigatti, SL Melvin, DL Williams, SC Raimondi and SB Murphy
We examined the arrangement of the mu heavy-chain immunoglobulin (Ig) genes
in the leukemic blast cell DNA of 93 children with acute lymphoblastic
leukemia (ALL). All cases met morphologic and cytochemical criteria for
ALL, lacked detectable T cell surface antigens, and expressed HLA-DR (Ia)
antigens. Eighty-three of the 93 patients (89%) were positive for the
common acute lymphoblastic leukemia antigen (CALLA), and 20 of 91 (22%)
tested had detectable cytoplasmic immunoglobulin. As expected, the
heavy-chain lg gene was rearranged in all cases, and the pattern of
rearrangements was variable; 23 had one allele rearranged and one in the
germ line configuration; 15 had one rearranged and one deleted; and 37 had
two rearranged. Unexpectedly, in 18 patients the presence of more than two
mu gene-hybridizing bands was detected. Combinations of enzymes and
heavy-chain gene probes were used to confirm that the extra bands were not
the result of underdigestion of the DNA or DNA restriction site
polymorphism. In eight of the 18 patients, we identified an extra
chromosome 14 as a possible cause of the extra bands' hybridizing to the mu
heavy-chain constant-region probe. In the remaining ten patients, the
presence of three or four bands hybridizing with the mu probe suggests the
presence of two populations of leukemic cells that may have arisen either
by separate leukemic transformation events or by clonal evolution of one
clone into two related lines. Although preliminary (2-year follow-up), our
data suggest that childhood ALL of B lineage with more than two mu
heavy-chain genes, but without extra copies of chromosome 14, may be more
resistant to therapy.
Volume 67,
Issue 3,
pp. 698-703,
03/01/1986
Copyright © 1986 by The American Society of Hematology
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