title: Combination of broad molecular screening and cytogenetic analysis for genetic risk assignment and diagnosis in patients with acute leukemia.
abstract: We evaluated the impact of genetic analysis combining cytogenetics and broad molecular screening on leukemia diagnosis according to World Health Organization (WHO) and on genetic risk assignment. A two-step nested multiplex RT-PCR assay was used that allowed the detection of 29 fusion transcripts. A total of 186 patients (104 males (56%), 174 adults (94%), 12 children (6%), 155 AML (83%), 31 ALL (17%)) characterized by morphology and immunophenotyping were included. Of these 186 patients, 120 (65%) had a genetic abnormality. Molecular typing revealed a fusion transcript in 49 (26%) patients and cytogenetic analysis revealed an abnormal karyotype in 119 (64%). A total of 27 (14%) cases were genetically classified as favorable, 107 (58%) intermediate and 52 (28%) unfavorable. For 38 (20%) patients, there was a discrepancy in the genetic risk assignments obtained from broad molecular screening and cytogenetics. Cryptic fusion transcripts in nine (5%) patients changed the genetic risk assignment in four and the WHO classification in four patients. In 34 patients (18%), cytogenetics defined the risk assignment by revealing structural and numerical chromosomal abnormalities not detected by molecular screening. Broad molecular screening and cytogenetics are complementary in the diagnosis and genetic risk assignment of acute leukemia.
authors.affiliation: Hematology, University Hospital Basel, Basel, Switzerland. meyers@uhbs.ch
authors.forename: S
authors.initials: S
authors.lastname: Meyer-Monard
authors.forename: V
authors.initials: V
authors.lastname: Parlier
authors.forename: J
authors.initials: J
authors.lastname: Passweg
authors.forename: D
authors.initials: D
authors.lastname: Mühlematter
authors.forename: U
authors.initials: U
authors.lastname: Hess
authors.forename: M
authors.initials: M
authors.lastname: Bargetzi
authors.forename: T
authors.initials: T
authors.lastname: Kühne
authors.forename: C
authors.initials: C
authors.lastname: Cabrol
authors.forename: A
authors.initials: A
authors.lastname: Gratwohl
authors.forename: M
authors.initials: M
authors.lastname: Jotterand
authors.forename: A
authors.initials: A
authors.lastname: Tichelli
mesh_terms: D000208:Acute Disease; D000328:Adult; D002051:Burkitt Lymphoma / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002869:Chromosome Aberrations; D015331:Cohort Studies; D020732:Cytogenetic Analysis / Q000379:methods*; D005260:Female; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018570:Risk Assessment; D014944:World Health Organization