Molecular detection and characterization of clonal cell populations in acute lymphocytic leukemia by analysis of conformational polymorphisms of cRNA molecules of rearranged T-cell-receptor-γ and immunoglobulin heavy-chain genes Journal Article
| Authors: | Koch, O. M.; Volkenandt, M.; Göker, E.; Buer, J.; Probst, M.; Banerjee, D.; Danenberg, P. V.; Bertino, J. R. |
| Article Title: | Molecular detection and characterization of clonal cell populations in acute lymphocytic leukemia by analysis of conformational polymorphisms of cRNA molecules of rearranged T-cell-receptor-γ and immunoglobulin heavy-chain genes |
| Abstract: | Junctional regions of rearranged T-cell-receptor-γ (TCR) and immunoglobulin heavy-chain (IgH) genes represent an idiotypic DNA sequence for an individual lymphocytic cell, and any clone or clonal disease developing from this cell. In this study, a novel methodology for detection and characterization of clone specific DNA sequences in patients with acute lymphocytic leukemia (ALL) was developed. Junctional regions of rearranged TCR-γ IgH genes in specimens of bone marrow aspirates of patients with ALL (precursor-B-ALL ten, T-ALL two, null-ALL one; ALL not classified one), of a patient with lymphoid blast crisis of chronic myeloid leukemia, of a B-cell chronic lymphocytic leukemia, and in DNA from peripheral blood mononuclear cells of ten healthy volunteers were amplified by polymerase chain reaction (PCR). The PCR products were transcribed into complementary RNA (cRNA). Conformational polymorphisms of cRNA molecules were analyzed by non-denaturing polyacrylamide gel electrophoresis. A specific cRNA banding pattern for rearranged TCR-γ or IgH genes was observed in all patients with lymphocytic leukemia. In contrast, analysis of DNA from healthy volunteers yielded a smear of confluent polymorphisms representing multiple different cRNA molecules. In two patients with precursor-B-ALL, cRNA banding patterns of junctional regions of rearranged TCR-γ genes were analyzed in sequential bone marrow aspirates. The banding patterns disappeared after chemotherapy and achievement of blast clearance. This novel and rapid molecular assay offers several advantages as compared to Southern blot analyses and previous PCR based methodologies for the detection of clonal lymphocytic populations. With this methodology, studies on the clonal evolution of lymphoproliferative disorders (e.g. the prognostic significance of the emergence of additional clones) can be performed more easily than with any other traditional molecular method. |
| Keywords: | cancer chemotherapy; clinical article; controlled study; human cell; methodology; polymerase chain reaction; cell population; chronic myeloid leukemia; t lymphocyte receptor gamma chain; immunoglobulin heavy chain; gene rearrangement; immunoglobulin gene; mononuclear cell; bone marrow biopsy; dna sequence; acute lymphocytic leukemia; cell clone; chronic lymphatic leukemia; complementary rna; polyacrylamide gel electrophoresis; dna polymorphism; blast cell crisis; rna conformation; t lymphocyte receptor gene; human; priority journal; article |
| Journal Title: | Leukemia |
| Volume: | 8 |
| Issue: | 6 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1994-06-01 |
| Start Page: | 946 |
| End Page: | 952 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 8207989 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- CODEN: LEUKE C2 -- Source: Scopus |
Citation Impact
Related MSK Work