title: ABL1 amplification in T-cell acute lymphoblastic leukemia.
abstract: ABL1 amplification, due to a cryptic episomal translocation NUP214/ABL1, is a novel finding in T-cell acute lymphoblastic leukemia (ALL). Here we report on the incidence and clinical features of this genetic defect in a series of 30 consecutive adult T-cell ALL patients. Multiple copies of the ABL1 gene were detected in two patients (6.6%), one with the karyotype 46,XY,t(1;3)(p36;p21),del(6)(q23)/46,XY and the other without analyzable metaphases. Metaphase/interphase fluorescence in situ hybridization (FISH) detected multiple uncountable signals corresponding to ABL1 in mitotic cells and nuclei from both patients. In one patient, no signals corresponded with the 9p21 chromosomal region, which contains the p16INK4a gene, and in the other one signal was observed. Quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) demonstrated that in these patients ABL1 gene expression was 14- and 18-fold greater than in normal controls, and returned to normal levels only when complete remission was achieved. We reached the following conclusions: (1) FISH is the only technique that promptly identifies T-cell ALL patients with ABL1 amplification, (2) quick identification with FISH is fundamental in the clinic because this T-cell ALL subset is imatinib sensitive but may become resistant due to development of additional mutations, and (3) ABL1 quantitative RT-PCR may be easily applied to monitor minimal residual disease.
authors.affiliation: Division of Hematology, IRCCS Policlinico San Matteo, University of Pavia, Piazzale Golgi No. 5, 27100 Pavia, Italy. p.bernasconi@smatteo.pv.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernasconi
authors.forename: Silvia
authors.initials: S
authors.lastname: Calatroni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Giardini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Inzoli
authors.forename: Carlo
authors.initials: C
authors.lastname: Castagnola
authors.forename: Paola Maria
authors.initials: PM
authors.lastname: Cavigliano
authors.forename: Barbara
authors.initials: B
authors.lastname: Rocca
authors.forename: Marina
authors.initials: M
authors.lastname: Boni
authors.forename: Jessica
authors.initials: J
authors.lastname: Quarna
authors.forename: Rita
authors.initials: R
authors.lastname: Zappatore
authors.forename: Marilena
authors.initials: M
authors.lastname: Caresana
authors.forename: Clara
authors.initials: C
authors.lastname: Bianchessi
authors.forename: Enrico Bobbio
authors.initials: EB
authors.lastname: Pallavicini
authors.forename: Mario
authors.initials: M
authors.lastname: Lazzarino
mesh_terms: D000368:Aged; D002648:Child; D005784:Gene Amplification; D016313:Genes, abl; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction