The genomic breakpoint in a patient with Philadelphia-positive acute leukemia is 5' of the breakpoint cluster region

Cancer Genet Cytogenet. 1988 Jun;32(2):217-27. doi: 10.1016/0165-4608(88)90284-1.


We report a case of acute leukemia in which studies at presentation showed both myeloid and lymphoid cell surface markers. At relapse membrane markers studies were consistent with a leukemia of B-lymphoid lineage. However, immunoglobulin (Ig) and T cell receptor (TCR) beta chain genes were both found in a rearranged configuration. The majority of metaphases from the leukemic cells at presentation showed the Philadelphia chromosome, t(9;22)(q34;q11), whereas a minority were normal. At relapse both Ph-positive and -negative metaphases were still present in the bone marrow but some of the Ph-negative metaphases had acquired an additional chromosome #19 [47,XY, + 19]. Southern analysis of DNA from leukemic bone marrow cells at diagnosis showed no rearrangement of breakpoint cluster region (bcr). There was no bcr-abl chimeric mRNA typical of Ph-positive chronic myeloid leukemia (CML). However, the cells expressed an abl-related protein of Mr 190 kd with enhanced tyrosine kinase activity. Leukemic cell metaphases were studied by the technique of in situ hybridization with probes for C-lambda, sis, abl, and 5' bcr. The c-abl probe mapped to chromosome 22q11 in Ph-positive metaphases. The 5' bcr probe mapped to 9q+ in the Ph-positive metaphases and the C-lambda gene mapped to the Ph chromosome. Thus, the genomic breakpoint in this patient must lie upstream of the BCR defined by study of Ph-positive CML and downstream of the C-lambda gene locus. We speculate that the Ph-negative cells in this patient may represent a leukemic proliferation susceptible to acquisition of specific chromosomal changes.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes
  • Bone Marrow / ultrastructure
  • Chromosome Aberrations*
  • Chromosome Banding
  • Chromosomes, Human, Pair 19
  • DNA / genetics
  • Female
  • Genetic Markers*
  • Humans
  • Karyotyping
  • Leukemia, Lymphoid / genetics*
  • Leukemia, Myeloid / genetics
  • Male
  • Multigene Family
  • Nucleic Acid Hybridization
  • Philadelphia Chromosome*


  • Genetic Markers
  • DNA