Prospective application of a multiplex reverse transcription‐polymerase chain reaction assay for the detection of balanced translocations in leukaemia: a single‐laboratory study of 390 paediatric and adult patients

• Published in: British journal of haematology 2004-10, Vol.127 (1), p.59-66
• Main Authors: Olesen, Lene Hyldahl, Clausen, Niels, Dimitrijevic, Andreja, Kerndrup, Gitte, Kjeldsen, Eigil, Hokland, Peter
• Format: Article
• Language: English
• Subjects: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; balanced translocations; Biological and medical sciences; Child; Child, Preschool; Chromosome Aberrations; cryptic translocations; Diagnosis, Differential; Hematologic and hematopoietic diseases; Hematology; Humans; Infant; Infant, Newborn; leukaemia; Leukemia - diagnosis; Leukemia - genetics; Leukemia, Myeloid - diagnosis; Leukemia, Myeloid - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical genetics; Medical sciences; Middle Aged; multiplex polymerase chain reaction; Myeloproliferative Disorders - diagnosis; Myeloproliferative Disorders - genetics; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction - methods; Translocation, Genetic
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2004.05161.x

Summary The upfront application of molecular methods for identifying the fusion transcripts arising from balanced translocations in haematopoietic malignancies has several advantages: sensitivity is independent of its frequency, i.e. rare ones are not missed, cytogenetically cryptic aberrations are identified and it provides a platform for minimal residual disease (MRD) detection. Employing a multiplex reverse transcription polymerase chain reaction (RT‐PCR) assay identifying 27 fusion transcripts we prospectively analysed blood and/or bone marrow samples from 390 patients referred for diagnosis and treatment for acute leukaemia and chronic myeloproliferative disorders (CMPD) from a geographically well‐defined region in Denmark. A total of 233 patients were diagnosed with acute myeloid leukaemia (AML), 95 with acute lymphoblastic leukaemia (ALL) origin and 62 patients were recorded as CMPD. Twenty‐three percent AML, 32% ALL and 55% CMPD patients exhibited chromosomal aberrations detected by the multiplex RT‐PCR. Cytogenetically cryptic translocations were seen in 15% of the cases. Conversely, the cytogenetic analysis identified chromosomal aberrations other than translocations in 45% of AML cases and 63% of ALL cases. We conclude that, while the fraction of translocation positive leukaemia patients in an unselected cohort is lower than hitherto believed, a molecular approach to their diagnosis is worthwhile, partly for identifying cryptic and rare translocations, partly for monitoring MRD.