title: Prognostic implications of breakpoint and lineage heterogeneity in Philadelphia-positive acute lymphoblastic leukemia: a review.
abstract: Philadelphia-positive (Ph) acute lymphoblastic leukemia (ALL) is heterogeneous both in terms of the BCR gene breakpoints (M-bcr and m-bcr) and in the number of cell lineages carrying the Ph chromosome. The impact of these observations on the controversy surrounding Ph ALL and Ph+ chronic granulocytic leukemia (CGL) is unclear. Twenty cases of Ph ALL (four newly investigated and 16 previously published) were classified into nine stem-cell (the Ph in myeloid and lymphoid cells) and 11 lymphoid-restricted cases. Lymphoid cases had a lower leucocyte count (56 x 10(9)/l) than stem-cell cases (151 x 10(9)/l) (p < 0.01). The M-bcr and m-bcr breakpoints (in 14 cases) were found in lymphoid (four cases of each) and stem-cell (five and one cases respectively) cases. Lymphoid cases had significantly shorter event-free survival (median 4 months) than stem-cell cases (median 35 months) (p < 0.01). M-bcr cases were older (mean 41 years) than m-bcr cases (mean 36 years)(p = NS); m-bcr cases had higher leukocyte counts (mean 85 x 10(9)/l) than M-bcr cases (36 x 10(9)/l)(p < 0.01) but breakpoint had no impact on prognosis. Lineage involvement, but not breakpoint, appears to distinguish prognostically important sub-groups of Ph ALL. Paradoxically, lymphoid-restricted cases have a worse prognosis than cases arising in a pluripotent stem-cell.
authors.affiliation: Department of Haematology, Royal Free Hospital and School of Medicine, London, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Secker-Walker
authors.forename: J M
authors.initials: JM
authors.lastname: Craig
mesh_terms: D000293:Adolescent; D000328:Adult; D001752:Blast Crisis / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D014178:Translocation, Genetic / Q000235:genetics*