Secondary chromosomal abnormalities in acute leukemias.

Secondary chromosomal aberrations reported in the literature were surveyed in acute myeloid or lymphoblastic leukemia (AML or ALL) with one of the following primary abnormalities: in AML, t(1;3), t(1;22), der(1;7), inv(3), t(3;5) +4, del(5q), t(6;9), -7, t(7;11), del(7q), +8, t(8;16), t(8;21), +9, t(9;11), del(9q), t(9;22), +11, del(11q), t(11;19), del(12p), +13, t(15;17), inv(16), t(16;21), i(17)(q10), del(20q), -21, +21, +22, and -Y; in ALL, t(1;14), t(1;19), der(19)t(1;19), t(4;11), del(6q), t(8;14)(q24;q11), t(8;14)(q24;q32), t(8;22), del(9p), dic(9;12), i(9)(q10), t(9;22), t(10;14), t(11;14), t(11;19), del(12p), -20, +21, and del(22q). Out of 7111 acute leukemias with clonal karyotypic aberrations, 2414 AMLs and 1078 ALLs had one of the selected primary chromosome rearrangements, and 40 and 49% of these AMLs and ALLs, respectively, displayed additional abnormalities. The type and frequency of these secondary changes were ascertained and then correlated with both the primary abnormality and the morphology or immunophenotype of the acute leukemia. The distribution of the secondary changes was clearly nonrandom. The most frequent numerical changes were -Y, -X, -7, +8, and +22 in AML and +X, +6, -7, +8, and +21 in ALL. The most common structural aberrations were del(5q), del(7q), and del(9q) in AML and dup(1q), i(7q)(q10), and der(22)t(9;22) in ALL. Some secondary changes were common to both disease groups, e.g. -7, +8, and +21, but several anomalies were restricted to either AML, such as -X, -5, and del(9q), or ALL, e.g. +X, i(7)(q10), and i(9)(q10). The type and frequency of the secondary aberrations varied within the AMLs and ALLs, not only among the different primary abnormality subgroups but also among the AML morphologies and the immunophenotypic maturation degrees of the ALLs. In general, the type of primary abnormality, rather than the differentiation stage of the acute leukemia, appeared to be instrumental in determining the type of secondary changes accruing. This conclusion was based on the finding that several primary abnormalities characterizing acute leukemias of the same morphology or immunophenotype displayed different patterns of secondary anomalies. The nonrandom, and sometimes quite specific, patterns of secondary aberrations strongly indicate that they are responsible for important phenotypic features of the tumor cell population, presumably closely associated with tumor progression. The molecular pathogenetic consequences of the secondary anomalies are unknown, but since most secondary changes are monosomies, trisomies, deletions, or isochromosomes resulting in genomic imbalances, one may hypothesize that gene dosage alterations rather than specific gene rearrangements are essential for tumor evolution.(ABSTRACT TRUNCATED AT 400 WORDS)