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Cytogenetics of childhood T-cell leukemia
SC Raimondi, FG Behm, PK Roberson, CH Pui, GK Rivera, SB Murphy and DL Williams
Department of Pathology and Laboratory Medicine, St Jude Children's
Research Hospital, Memphis, TN 38101.
The karyotypes of 57 cases of childhood T-cell acute lymphoblastic leukemia
(ALL) were analyzed to establish the cytogenetic profile in this disease.
Three questions were of particular interest. Do the chromosomal changes in
T-cell ALL preferentially affect bands where genes encoding the T-cell
receptor for antigen (TCR) have been mapped? Do alterations involving the
TCR gene regions appear with any notable frequency in B-progenitor ALL? Do
chromosomal abnormalities in this disease relate to stage of T-cell
ontogeny? A relatively high proportion of cases (65%) had a pseudodiploid
karyotype at presentation, the majority (58%) characterized by a
translocation. The overall frequency of translocations was 44%, comparable
to that among all banded cases of ALL seen in our laboratory. Hypodiploidy
and hyperdiploidy were exceedingly rare (only four of 57 cases); 16 cases
(28%) had apparently normal karyotypes. In half the cases with a
translocation (14 of 24), the breakpoints were in regions to which the
alpha and beta chain TCR genes have been mapped. Chromosomal breakpoints
that were consistently observed in the vicinity of TCR gene loci were
7q32-q36 (TCR beta chain; n = 8), 14q11-q13 (TCR alpha chain; n = 6); other
frequent breakpoints were 9p13-pter (n = 8) and 6q15-qter (n = 9).
Chromosomal alterations occurred near TCR gene loci significantly more
often in T-cell cases than in a comparison group of 335 patients with
B-cell precursor ALL (26% v 1.5%, P = .0001). Stage I thymocyte development
(CD7+, CD2+, CD5+, CD1-, CD3-, CD4-, CD8-) was noted in 23 cases, stage II
(CD7+, CD2+, CD5+, CD1+, CD3-, CD4 +/-, CD8 +/-) in 25 cases, and stage III
(CD9+, CD2+, CD1-, CD5+, CD3+, and either CD4+ or CD8+) in nine cases. The
only statistically significant associations between cytogenetic findings
and T-cell ontogeny were a higher frequency of normal karyotypes in cases
with stage I thymocytes, and of pseudodiploidy in stage II cases. There was
no apparent relationship between particular translocations and level of
thymocyte maturation. Our findings indicate that most children with T-cell
ALL have pseudodiploid karyotypes, although a surprisingly high percentage
lack demonstrable abnormal clones. Specific chromosomal changes do not
appear to be related to discrete stages of T-cell ontogeny as defined in
this study, but they occur preferentially in bands containing TCR genes.
Volume 72,
Issue 5,
pp. 1560-1566,
11/01/1988
Copyright © 1988 by The American Society of Hematology
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