title: E2A/HLF fusion cDNAs and the use of RT-PCR for the detection of minimal residual disease in t(17;19)(q22;p13) acute lymphoblastic leukemia.
abstract: Three cases of acute lymphoblastic leukemia (ALL) with the rare t(17;19)(q22;p13) translocation were investigated for E2A/HLF fusion genes using reverse transcription coupled with polymerase chain reaction (RT-PCR). The patients had C-ALL, F/17 years (case 1) or pre-B ALL, M/11 years (case 2) and M/13 years (case 3). Case 1 had an event-free survival (EFS) of 42 months. Case 2 was ultimately refractory to treatment. Case 3 presented following EFS of 16 months in morphological remission (1% blasts), but with immunological and cytogenetic evidence of active disease, then relapsed, remitted and relapsed. Type II E2A/HLF fusion cDNA was found at diagnosis (cases 1, 2), at presentation (case 3) and in all samples tested, whether with active disease or in complete remission (CR). Case 3 showed, in addition, type I fusion E2A/HLF cDNA at presentation, through induction therapy when there was evidence of active disease, but not in CR. Cases 1 and 3 had bone marrow transplantation while in CR but with residual disease detectable by RT-PCR. All patients have died of ALL. Two cases (2 and 3) had hypercalcemia with bone lesions. No case had any evidence of disseminated intravascular coagulation. This is the first demonstration of the value of RT-PCR for the detection of minimal residual disease in t(17;19) ALL.
authors.affiliation: Department of Haematology, Royal Free Hospital School of Medicine, London, UK.
authors.forename: P E
authors.initials: PE
authors.lastname: Devaraj
authors.forename: L
authors.initials: L
authors.lastname: Foroni
authors.forename: M
authors.initials: M
authors.lastname: Sekhar
authors.forename: T
authors.initials: T
authors.lastname: Butler
authors.forename: F
authors.initials: F
authors.lastname: Wright
authors.forename: A
authors.initials: A
authors.lastname: Mehta
authors.forename: D
authors.initials: D
authors.lastname: Samson
authors.forename: H G
authors.initials: HG
authors.lastname: Prentice
authors.forename: A V
authors.initials: AV
authors.lastname: Hoffbrand
authors.forename: L M
authors.initials: LM
authors.lastname: Secker-Walker
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D015139:Blotting, Southern; D002648:Child; D002886:Chromosomes, Human, Pair 17; D002888:Chromosomes, Human, Pair 19; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012194:RNA-Directed DNA Polymerase; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C076554:E2a-Hlf fusion protein, human; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D012194:RNA-Directed DNA Polymerase