TY - JOUR
T1 - Array comparative genome hybridization analysis of acute lymphoblastic leukaemia and acute megakaryoblastic leukaemia in patients with Down syndrome
AU - Lo, Ken C.
AU - Chalker, Jane
AU - Strehl, Sabine
AU - Neat, Michael
AU - Smith, Owen
AU - Dastugue, Nicole
AU - Kearney, Lyndal
AU - Izraeli, Shai
AU - Kempski, Helena
AU - Cowell, John K.
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/9
Y1 - 2008/9
N2 - Twenty-five cases of B-cell precursor acute lymphoblastic leukaemia (ALL) from Down syndrome (DS) patients were analyzed using array comparative genomic hybridization (aCGH) and compared with two other subgroups of non-DS patients with ALL; five cases with high-hyperdiploidy (HH) and nine cases with ETV6-RUNX1 positive clones. Seven cases of DS-acute megakaryoblastic leukaemia (AMKL) were also included, DS-ALL cases showed relatively stable karyotypes with cryptic losses and gains that most frequently involved chromosomes X, 1, 2, 9, 11, 16, and 17. The most consistent change involved a deletion in 2p, spanning region Chr2:88273220-91084234, which in some cases appeared to be homozygous. ALL from non-DS patients showed a similar overall karyotypic stability, although gains of chromosome 21 were infrequent in the ETV6-RUNX1 positive cases. The most consistent change in this group involved a 12p deletion, where Chr12:10383878-16017619 defined the common region of overlap. All HH-ALL karyotypes showed variable gains of chromosome 21. This overall analysis supports the suggestion that, although constitutional trisomy 21 predisposes to ALL/AMKL, the cytogenetic changes associated with DS-ALL in particular, are most similar to those found in non-DS ETV6-RUNX1 positive ALL. The HH-ALL group, however, undergoes distinct karyotypic evolution not dependent on chromosome translocation/deletion events.
AB - Twenty-five cases of B-cell precursor acute lymphoblastic leukaemia (ALL) from Down syndrome (DS) patients were analyzed using array comparative genomic hybridization (aCGH) and compared with two other subgroups of non-DS patients with ALL; five cases with high-hyperdiploidy (HH) and nine cases with ETV6-RUNX1 positive clones. Seven cases of DS-acute megakaryoblastic leukaemia (AMKL) were also included, DS-ALL cases showed relatively stable karyotypes with cryptic losses and gains that most frequently involved chromosomes X, 1, 2, 9, 11, 16, and 17. The most consistent change involved a deletion in 2p, spanning region Chr2:88273220-91084234, which in some cases appeared to be homozygous. ALL from non-DS patients showed a similar overall karyotypic stability, although gains of chromosome 21 were infrequent in the ETV6-RUNX1 positive cases. The most consistent change in this group involved a 12p deletion, where Chr12:10383878-16017619 defined the common region of overlap. All HH-ALL karyotypes showed variable gains of chromosome 21. This overall analysis supports the suggestion that, although constitutional trisomy 21 predisposes to ALL/AMKL, the cytogenetic changes associated with DS-ALL in particular, are most similar to those found in non-DS ETV6-RUNX1 positive ALL. The HH-ALL group, however, undergoes distinct karyotypic evolution not dependent on chromosome translocation/deletion events.
KW - Acute lymphoblastic leukaemia
KW - Acute megakaryoblastic leukaemia
KW - Comparative genomic hybridization
KW - Down syndrome
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U2 - 10.1111/j.1365-2141.2008.07280.x
DO - 10.1111/j.1365-2141.2008.07280.x
M3 - Article
C2 - 18557744
AN - SCOPUS:50049121331
SN - 0007-1048
VL - 142
SP - 934
EP - 945
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 6
ER -