title: TEL/AML1 rearrangement and the prognostic significance in childhood acute lymphoblastic leukemia in Hong Kong.
abstract: The TEL/AML1 rearrangement has been implicated as an independent good prognostic factor in pediatric acute lymphoblastic leukemia (ALL). We examined TEL/AML1 using nested reverse-transcription polymerase chain reaction (RT-PCR) and correlated TEL/AML1 with cytogenetics and immunophenotypes in 75 consecutively analyzed Chinese children with ALL in Hong Kong. TEL/AML1 was detected in 17.9% (12/67) B-lineage ALL at diagnosis but not in 8 T-ALL children or in 34 adults with ALL. E2A/PBX1, MLL/AF4, and BCR/ABL were not found in TEL/AML1+ patients. Coexpression of cross-lineage antigens was associated with TEL/AML1 gene fusion (p = 0.032), with CD13 in 80% (4/5) TEL/AML1+ cohort. Chromosomal abnormalities were demonstrated in 50% of the TEL/AML1+ ALL; however, a cryptic t(12;21) was not detected in these cases. Hyperdiploidy of 47-48 chromosomes was encountered in 25%. Deletion of 12p resulting in the loss of the normal allele of TEL and nonspecific del(6q) were noted in 8% (1/12) and 25% (3/12) of the TEL/AML1+ children, respectively. Rapid clearance of TEL/AML1 was noted in 50% of the patients on completion of the induction therapy; however, 16.7% (2/12) TEL/AML1+ ALL relapsed at a mean of 48.6 months from diagnosis (25 months off-therapy). The incidence of relapses of TEL/AML1+ ALL was comparable to that at diagnosis in B-lineage ALL (14.3% [2/14] vs. 17.9% [12/67], p > 0.05). The relapse rate in TEL/AML1+ ALL was similar to that of TEL/AML1- ALL (16.7% [2/12] vs. 20.6% [13/63], p > 0.05). The duration of first complete remission in TEL/AML1+ ALL was significantly longer as compared to TEL/AML1- ALL (mean [range] in month: 48.6 [47.2 - 50] vs 14.6 [2.9 - 42.3], p < 0.0001). Irrespective of TEL/AML1 rearrangement, the probabilities of the five-year overall survival and the event-free survival of patients were comparable (overall survival: 100% vs. 72.3%, p = 0.166 and event-free survival: 60% vs. 56.2%, p = 0.343). Our data would not suggest a less aggressive treatment regimen for TEL/AML1+ ALL.
authors.affiliation: Hematology and Bone Marrow Transplantation Division, Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: K S
authors.initials: KS
authors.lastname: Tsang
authors.forename: C K
authors.initials: CK
authors.lastname: Li
authors.forename: K W
authors.initials: KW
authors.lastname: Chik
authors.forename: M M
authors.initials: MM
authors.lastname: Shing
authors.forename: W C
authors.initials: WC
authors.lastname: Tsoi
authors.forename: M H
authors.initials: MH
authors.lastname: Ng
authors.forename: T T
authors.initials: TT
authors.lastname: Lau
authors.forename: Y
authors.initials: Y
authors.lastname: Leung
authors.forename: P M
authors.initials: PM
authors.lastname: Yuen
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit; D003582:Cytogenetics; D005260:Female; D015321:Gene Rearrangement; D005820:Genetic Testing; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein