Detection of Minimal Residual Disease in Acute Lymphoblastic Leukemia Patients by Polymerase Chain Reactions
Significant progress has been achieved in the treatment of acute lymphoblastic leukemia (ALL) by the introduction of modern chemotherapeutic strategies . However, disease relapse following successful remission induction still poses a major clinical challenge. The quantity and kinetic behavior of residual leukemic cells remains largely enigmatic due to the limitation of most currently available techniques to identify less than 1%–5% neoplastic cells in the population being examined . The use of double-color immunofluorescence has markedly improved the sensitivity with which persisting disease can be detected in distinct leukemias characterized by phenotypic features that are extremely rare or absent on normal hematopoietic counterparts . More recently the development of polymerase chain reaction (PCR) strategies has opened a new era in the analysis of minimal residual disease by allowing the identification of neoplastic cells at a 10−4 to 10−6 level . In the following we will summarize our experience with the application of PCR techniques in monitoring ALL patients during the course of the disease.
KeywordsLeukemia Recombination Agarose Bromide Oligomer
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- 2.Hagenbeek A, Löwenberg B (eds) (1986) Minimal residual disease in acute leukemia. Nijhoff, DordrechtGoogle Scholar
- 5.Hansen-flagge TE, Yokota S, Bartram CR (1989) Detection of minimal residual disease in acute lymphoblastic leukemia by in vitro amplification of rearranged T-cell receptor ô chain sequences. Blood 74: 1762–1767Google Scholar
- 7.Yamada M, Hudson S, Tournay O. Bitten-bender S, Shane SS, Lange B, Tsujimoto Y, Caton AJ, Rovera G (1989) Detection of minimal disease in hematopoietic malignancies of the B-cell lineage by using thirdcomplementarity-determining region (CDR-III) specific probes. Proc Natl Acad Sci USA 15. 86: 5123–5127Google Scholar
- 12.Macintyre EA, d’Auriol L, Duparc N, Leverger G, Galibert F, Sigaux F (1990) Use of oligonucleotide probes directed against Teell antigen receptor gamma delta variable(diversity)-joining junctional sequences as a general method for detecting minimal residual disease in acute lymphoblastic leukemias. J Clin Invest 86: 2125–2135PubMedCrossRefGoogle Scholar
- 13.Raghavachar A,Thiel E, Bartram CR (1987) Analyses of phenotype and genotype in acute lymphoblastic leukemias at first presentation and in relapse. Blood 70: 1079–1083Google Scholar
- 15.Kurzrock R, Gutterman JU,Talpaz M (1988) The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med 319: 990–998Google Scholar
- 16.Maurer J, Janssen JWG, Thiel E, van Den-deren J, Ludwig WD, Aydemir Ü, Heinze B, Fonatsch C, Harbott J, Reiter A, Riehm H, Hoelzer D, Bartram CR (1991) Detection of chimeric BCR-ABL genes in acute lymphoblastic leukaemia by polymerase chain reaction: frequency and clinical relevance. Lancet 337: 1055–1058PubMedCrossRefGoogle Scholar