title: 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.
abstract: 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.
authors.affiliation: Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lene Hyldahl
authors.initials: LH
authors.lastname: Olesen
authors.forename: Niels
authors.initials: N
authors.lastname: Clausen
authors.forename: Andreja
authors.initials: A
authors.lastname: Dimitrijevic
authors.forename: Gitte
authors.initials: G
authors.lastname: Kerndrup
authors.forename: Eigil
authors.initials: E
authors.lastname: Kjeldsen
authors.forename: Peter
authors.initials: P
authors.lastname: Hokland
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D003937:Diagnosis, Differential; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000175:diagnosis / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000235:genetics; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014178:Translocation, Genetic