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 malignant myeloid diseases by using fluorescence in situ hybridization (FISH) with phage and cosmid probes mapped and ordered on 11q22-24. Two of the four patients had non-Hodgkin's lymphoma or acute lymphoblastic leukemia as the primary malignancy and had received cytotoxic chemotherapy, including topoisomerase II inhibitors. The other two had de novo acute myeloid leukemia or myelodysplastic syndrome. FISH analysis showed that all 11q breakpoints were located centromeric to the MLL gene and between cosmids CN2900 and CN1323. We identified a yeast artificial chromosome (YAC) clone that spanned the inv(11) breakpoints on 11q. From this YAC, we identified a P1 clone, which included the breakpoints in at least three of the four patients. It is highly likely that the same gene on the P1 clone is rearranged in leukemic cells of each patient. This gene may be one of the targets for topoisomerase II inhibitors.
Kobayashi
H
H
Third Clinical Department, Saitama Cancer Center Hospital, Japan.
Arai
Y
Y
Hosoda
F
F
Maseki
N
N
Hayashi
Y
Y
Eguchi
H
H
Ohki
M
M
Kaneko
Y
Y
D000293:Adolescent; D000328:Adult; D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy / Q000209:etiology / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology*; D017101:Bacteriophage P1; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D007446:Chromosome Inversion; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D015698:Genomic Library; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000209:etiology / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000209:etiology / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000209:etiology / Q000235:genetics; D059005:Topoisomerase II Inhibitors
D059005:Topoisomerase II Inhibitors