Preponderant mitotic activity of nonleukemic cells plays an important role in failures to detect abnormal clone in childhood acute lymphoblastic leukemia.

Abstract

At diagnosis, clonal chromosomal abnormalities are found in the bone marrow blasts in more than two thirds of children with acute lymphoblastic leukemia (ALL). Practically, however, failure to detect these abnormalities is frequent and usually attributed to poor marrow sampling, inadequate metaphases, and/or a preponderant mitotic activity among nonleukemic cells. The authors applied fluorescence in situ hybridization (FISH) techniques to re-examine 30 cases of karyotypically "normal" childhood ALL to explore the role of preponderant mitotic activities of nonleukemic cells in failures to detect clonal abnormalities. The FISH test were performed using TEL/AML1 fusion gene probe and the centromere probes for chromosome 8 and 10 to detect the t(12;21) translocation and/or hyperdiploidy. Half of the karyotypically "normal" ALL cases examined have been found to have abnormal clones with t(12;21) rearrangement and/or hyperdiploidy by this specially designed FISH assay. Contrary to expectation, the authors found a higher incidence (52%) of clonal abnormalities in cases where over 20 metaphases had been examined than in cases (44%) where fewer than 20 metaphases had been analyzed. These findings suggest that a preponderant mitotic activity of nonleukemic cells plays an important role in failures to detect an abnormal clone by conventional cytogenetic studies. Therefore, karyotypically "normal" childhood ALL patients should undergo FISH studies to rule out the presence of t(12;21) and/or hyperdiploid clone.