SECONDARY ACUTE LEUKEMIAS WITH 11Q23 REARRANGEMENT - CLINICAL, CYTOGENETIC, FISH AND FICTION STUDIES

Three patients with secondary acute leukaemia after treatment with top oisomerase II inhibitor agents are described. Two patients had acute m yeloid leukaemia (AML), FAB M5a, one had pro-B-acute lymphoblastic leu kaemia (ALL). The interval between initiation of chemotherapy and the onset of secondary acute leukaemia was 19-20 months. 11q23 rearrangeme nts were detected in all cases, They were due to translocations t(11;1 9) (q23;p13.3), t(11;16)(q23;p13) and t(4;11)(q21;q23), respectively. Fluorescence in situ hybridization (FISH) with Yeast Artificial Chromo some (YAC) probe 13HH4 spanning the ALL-1 gene on 11q23 confirmed that in each case the ALL-1 gene had been disrupted by the translocations. The study underlined the relationship between the development of seco ndary acute leukaemias with 11q23 rearrangement and previous chemother apy with topoisomerase II inhibitor agents. So far, however, only six adult patients with secondary ALL with t(4;11) after treatment with to poisomerase II inhibitor agents have been reported. ALL with t(4;11) m ostly occurs in infants or young children. Our patient received epirub icin continuously for >19 months. This indicates that both myeloid and lymphoid leukaemias with involvement of the ALL-1 gene can be induced by exogenous agents, especially topoisomerase II inhibitors. Thus the y may have a common biological background. This hypothesis was substan tiated by means of combined immunophenotyping and FISH (FICTION). In t he case of AML M5a with t(11;19), the tumour cells with ALL-1 rearrang ement expressed CD34. Moreover, the pro-B-ALL with t(4;11) was CD34 po sitive. These findings suggest that the cell of origin of secondary AM L and ALL with 11q23 rearrangement is an immature haemopoietic progeni tor cell.