INVERSION OF CHROMOSOME-11, INV(11)(P15Q22), AS A RECURRING CHROMOSOMAL ABERRATION ASSOCIATED WITH DE-NOVO AND SECONDARY MYELOID MALIGNANCIES - IDENTIFICATION OF A P1 CLONE SPANNING THE 11Q22 BREAKPOINT

We studied four patients with inv(11)(p15q22) associated with malignan t myeloid diseases by using fluorescence in situ hybridization (FISH) with phage and cosmid probes mapped and ordered on 11q22-24. Two of th e four patients had non-Hodgkin's lymphoma or acute lymphoblastic leuk emia as the primary malignancy and had received cytotoxic chemotherapy , including topoisomerase II inhibitors. The other Mo had de novo acut e myeloid leukemia or myelodysplastic syndrome. FISH analysis showed t hat all I Iq breakpoints were located centromeric to the MLL gene and between cosmids CN2900 and CN1323. We identified a yeast artificial ch romosome (YAC) clone that spanned the inv(11) breakpoints on 11q. From this YAC, we identified a PI clone, which included the breakpoints in at least three of the four patients. It is highly likely that the sam e gene on the PI clone is rearranged in leukemic cells of each patient . This gene may be one of the targets for topoisomerase II inhibitors. (C) 1997 Wiley-Liss, Inc.