Biology and clinical significance of cytogenetic abnormalities in childhood acute lymphoblastic leukemia

Abstract

Virtually all cases of childhood ALL have chromosomal abnormalities and half contain translocations, which are nearly equally divided between random and nonrandom rearrangements. Nonrandom chromosomal abnormalities have been correlated with leukemic cell lineage, the degree of cell differentiation, and the specific gene involved at the molecular level. Many cytogenetic findings have prognostic significance; however, the adverse influence of certain changes, including most chromosomal translocations, may in fact be offset by the greater cytoreductive effects of intensified therapy. Table 4 summarizes the relation of selected karyotypic findings to treatment outcome in patients treated on contemporary protocols. Among all of the chromosomal abnormalities identified in childhood ALL, hyperdiploidy greater than 50 has been associated with the most favorable prognosis. At the opposite end of the spectrum, the treatment outcome for patients with classical Ph+ or hypodiploid ALL is very poor even in programs of intensive chemotherapy; alternative treatment such as bone marrow transplantation should be considered for such patients. Cases with the t(4;11)(q21;q23) also have a very poor clinical outcome, but the adverse prognosis may be limited to the infant or adolescent age groups. The prognostic significance of other nonrandom translocations, such as t(1;19)(q23;p13) and several other abnormalities, needs to be further assessed in larger numbers of patients. Finally, as more is learned about the molecular pathology underlying these rearrangements, it may be possible to develop new therapeutic agents that are specifically targeted to interfere with the aberrant gene products expressed by human leukemic cells.