title: Karyotyping, FISH, and PCR in acute lymphoblastic leukemia: competing or complementary diagnostics?
abstract: BACKGROUND
  Chromosomal abnormalities, such as t(9;22)(q34;q11) (ABL/BCR), t(12;21)(p13;q22) (TEL/AML1), and t(11q23) (MLL) are independent prognostic indicators in childhood acute lymphoblastic leukemia resulting in risk adapted therapy. Accurate and rapid detection of these abnormalities is mandatory, which is achieved by karyotyping, fluorescence in situ hybridization, and real time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR). For cost-effective diagnostic approaches knowledge of diagnostic accuracy of these tests is required. Therefore, we aimed to determine the diagnostic accuracy of karyotyping, fluorescence in situ hybridization, and RQ-PCR analysis.
  
  
  METHODS
  Retrospective study conducted between January 1, 1992 and January 1, 2007 in the Emma Children Hospital in Amsterdam. All consecutive patients under 18 years with acute lymphoblastic leukaemia were included. Diagnostic tests were performed according to international standards.
  
  
  RESULTS
  Diagnostic techniques show a high-reciprocal agreement and have a high-individual diagnostic accuracy in detecting the above-mentioned chromosomal translocations. However, the sensitivity of karyotyping for detecting the TEL-AML1 fusion gene and the sensitivity of RQ-PCR for detecting MLL-rearrangements was rather low.
  
  
  CONCLUSIONS
  Diagnostic accuracy of tests for detecting t(9;22), t(12;21), and t(11q23) is generally high, although sensitivity is not optimal for all anomalies. Despite the high-diagnostic accuracy, all diagnostic techniques should be used complementary, because any detection of a (significant) chromosomal aberration irrespective of diagnostic mode has to be considered in therapy.
authors.affiliation: Department of Paediatric Oncology, Emma Children Hospital AMC, University of Amsterdam, The Netherlands.
authors.forename: Louise
authors.initials: L
authors.lastname: Olde Nordkamp
authors.forename: Clemens
authors.initials: C
authors.lastname: Mellink
authors.forename: Ellen
authors.initials: E
authors.lastname: van der Schoot
authors.forename: Henk
authors.initials: H
authors.lastname: van den Berg
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics*; D012189:Retrospective Studies; D014178:Translocation, Genetic / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; C113855:MLL-AF4 fusion protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein