title: The genomic breakpoint in a patient with Philadelphia-positive acute leukemia is 5' of the breakpoint cluster region.
abstract: 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.
authors.affiliation: MRC Leukaemia Unit, Royal Postgraduate Medical School, London, England.
authors.forename: F
authors.initials: F
authors.lastname: Rassool
authors.forename: L
authors.initials: L
authors.lastname: Foroni
authors.forename: A
authors.initials: A
authors.lastname: Rahemtulla
authors.forename: O
authors.initials: O
authors.lastname: Dreazen
authors.forename: L
authors.initials: L
authors.lastname: Wiedemann
authors.forename: A P
authors.initials: AP
authors.lastname: Guo
authors.forename: S
authors.initials: S
authors.lastname: Legon
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
authors.forename: L
authors.initials: L
authors.lastname: Luzzatto
authors.forename: J
authors.initials: J
authors.lastname: Goldman
mesh_terms: D000328:Adult; D001402:B-Lymphocytes; D001853:Bone Marrow / Q000648:ultrastructure; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002888:Chromosomes, Human, Pair 19; D004247:DNA / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007621:Karyotyping; D007945:Leukemia, Lymphoid / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics; D008297:Male; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D010677:Philadelphia Chromosome
chemical_list: D005819:Genetic Markers; D004247:DNA