title: Variable Philadelphia breakpoints and potential lineage restriction of bcr rearrangement in acute lymphoblastic leukemia.
abstract: Philadelphia (Ph1) chromosome breakpoints in acute lymphoblastic leukemia (ALL) are of two kinds: those within the breakpoint cluster region (bcr+), as in chronic myeloid leukemia (CML), and those outside it (bcr-). These encode different c-abl messenger RNAs (mRNAs), p210 and p190, respectively. It has been suggested that one class of Ph+ ALL (bcr+) may be a variant of CML arising in a multipotent stem cell, the other (bcr-) de novo ALL initiated in a lymphoid-committed progenitor. Thirty-two cases of ALL (12 Ph1+, ten chromosomally normal, and ten non-mitotic cases) were investigated for bcr involvement. Breakpoints were found within five Ph1+ and in one normal case. There was no difference in clinical features, common ALL antigen (CALLA) positivity, cytogenetics, or response to treatment between the 6 bcr+ and 7 Ph1+ bcr- patients. Myeloid antigen expression was found in 2 bcr+ cases. Bcr rearrangement appeared to be restricted to the lymphoblastic component of marrow or blood in at least four bcr+ cases. In one case, separated myeloid and lymphoid cell fractions were both bcr+. Potential heterogeneity of the Ph1+ target cell, as seen in this study, may be more important in determining disease outcome than the precise location of the Ph breakpoint.
authors.affiliation: Department of Haematology, Royal Free Hospital School of Medicine, London, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Secker-Walker
authors.forename: H M
authors.initials: HM
authors.lastname: Cooke
authors.forename: P J
authors.initials: PJ
authors.lastname: Browett
authors.forename: C A
authors.initials: CA
authors.lastname: Shippey
authors.forename: J D
authors.initials: JD
authors.lastname: Norton
authors.forename: E
authors.initials: E
authors.lastname: Coustan-Smith
authors.forename: A V
authors.initials: AV
authors.lastname: Hoffbrand
mesh_terms: D005803:Genes, Immunoglobulin; D006801:Humans; D007945:Leukemia, Lymphoid / Q000235:genetics* / Q000276:immunology; D005810:Multigene Family; D010677:Philadelphia Chromosome; D011995:Recombination, Genetic