title: Cell lineage specific involvement in acute promyelocytic leukaemia (APL) using a combination of May-Grünwald-Giemsa staining and fluorescence in situ hybridization techniques for the detection of the translocation t(15;17)(q22;q12).
abstract: Acute promyelocytic leukaemia (APL) is strongly associated with the translocation t(15;17) which therefore provides a reliable marker to assess the potential involvement of different cell lineages. Six cases with morphologically, cytogenetically and molecularly proven APL were analysed at diagnosis or relapse by combining fluorescence in situ hybridization (FISH) with standard May-Grünwald-Giemsa (MGG) staining at the single cell level on bone marrow and blood smears. With the FICTION technique, combining immunophenotyping with FISH, haemopoietic precursor cells were identified using monoclonal antibodies against CD34, B- and T-lymphocytes could be identified with CD19 and CD3. In addition, HLA-DR-positive cells were studied for the presence of t(15;17). Morphologically identified myeloblasts were relocated on the smear after FISH and were found to be PML/RARA positive in 91%, abnormal promyelocytes in 97%. In contrast, a positive signal was obtained in only 18% of PMN. Erythroblasts, lymphocytes and plasma cells did not show a PML/RARA rearrangement. Accordingly, all cells expressing CD3 or CD19 were PML/RARA negative. CD34 positive precursor cells identified by FICTION were PML/RARA positive in 97%. HLA-DR-positive cells contained a PML/RARA rearrangement in 24% of cells in one case and were negative in the two other cases investigated. These data indicate that APL appears to originate from a level of haemopoietic precursor cells but is restricted to the myeloid lineage. The low proportion of PML/RARA-positive PMN points to the impairment of blast cell differentiation beyond the promyelocyte stage but also emphasizes the existence of normal residual haemopoietic stem cells from which PML/RARA-negative PMN must be derived.
authors.affiliation: Department of Haematology and Oncology, University of Göttingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Haferlach
authors.forename: H
authors.initials: H
authors.lastname: Löffler
authors.forename: C
authors.initials: C
authors.lastname: Nickenig
authors.forename: L
authors.initials: L
authors.lastname: Ramm-Petersen
authors.forename: M
authors.initials: M
authors.lastname: Meeder
authors.forename: R
authors.initials: R
authors.lastname: Schoch
authors.forename: B
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: S
authors.initials: S
authors.lastname: Schnittger
authors.forename: C
authors.initials: C
authors.lastname: Schoch
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
mesh_terms: D000328:Adult; D000368:Aged; D001399:Azure Stains; D019070:Cell Lineage; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D014178:Translocation, Genetic
chemical_list: D001399:Azure Stains