title: Expression of TEL-AML1 fusion transcripts and response to induction therapy in standard risk acute lymphoblastic leukemia.
abstract: We prospectively examined the frequency of the t(12;21)TEL-AML1 fusion in 504 children with newly diagnosed standard risk ALL using RT-PCR assays. Cells from 95 patients (18.8%) were TEL-AML1+. There was a significantly higher frequency of pseudodiploidy among the TEL-AML1+ cases (39.4% versus 14.1%, P = 0.001), primarily because structural abnormalities involving 12p and del(6q) occurred more frequently in the TEL-AML1+ group. TEL-AML1+ ALL was more sensitive to the induction chemotherapy than TEL-AML1- ALL. The percentage of "rapid early responders", i.e., patients who achieved an M1 (< 5% blasts) or M2 (5-25% blasts) marrow status on day 7 of induction chemotherapy, was significantly higher among TEL-AML1+ cases. The quality of remission of RT-PCR positive cases was excellent, as evidenced by the very low to absent MRD burden of their end-of-induction bone marrow specimens. TEL-AML1+ patients also had an excellent early EFS outcome. The probability of EFS at 30 months from study entry were 98.9 +/- 1.0% for the TEL-AML1+ group and 92.1 +/- 1.5% for the TEL-AML1- group (P = 0.0001). This prospective study significantly expands the knowledge gained from previous studies regarding the prognostic significance of t(12;21)TEL-AML1 fusion in pediatric ALL.
authors.affiliation: Children's Cancer Group ALL Biology Reference Laboratory, Parker Hughes Institute, 2665 Long Lake Road, Suite 300, St. Paul, MN 55113, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
authors.forename: N
authors.initials: N
authors.lastname: Pallisgaard
authors.forename: P
authors.initials: P
authors.lastname: Hokland
authors.forename: C
authors.initials: C
authors.lastname: Navara
authors.forename: R
authors.initials: R
authors.lastname: Narla
authors.forename: P S
authors.initials: PS
authors.lastname: Gaynon
authors.forename: H
authors.initials: H
authors.lastname: Sather
authors.forename: N
authors.initials: N
authors.lastname: Heerema
mesh_terms: D001853:Bone Marrow / Q000187:drug effects; D002648:Child; D050676:Core Binding Factor Alpha 2 Subunit; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D006801:Humans; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein