Frequency and clinical significance of cytogenetic abnormalities in pediatric T-lineage acute lymphoblastic leukemia: a report from the Children's Cancer Group.

PURPOSE Nonrandom chromosomal translocations are frequently observed in pediatric patients with acute lymphoblastic leukemia (ALL). Specific translocations, such as t(4;11) and t(9;22), identify subgroups of B-lineage ALL patients who have an increased risk of treatment failure. The current study was conducted to determine the prognostic significance of chromosomal translocations in T-lineage ALL patients. MATERIALS AND METHODS The study included 169 children with newly diagnosed T-lineage ALL enrolled between 1988 and 1995 on risk-adjusted protocols of the Children's Cancer Group (CCG) who had centrally reviewed cytogenetics data. Outcome analyses used standard life-table methods. RESULTS Presenting features for the current cohort were similar to those of concurrently enrolled patients for whom cytogenetic data were not accepted on central review. The majority of patients (80.5%) were assigned to CCG protocols for high-risk ALL and 86.4% had pseudodiploid (n = 80) or normal diploid (n = 66) karyotypes; modal chromosome number was not a significant prognostic factor. Overall, 103 of 169 (61%) patients had an abnormal karyotype, including 31 with del(6q), 29 with 14q11 breakpoints, 15 with del(9p), 11 with trisomy 8, nine with 11q23 breakpoints, nine with 14q32 translocations, and eight with 7q32-q36 breakpoints. Thirteen patients had the specific 14q11 translocation t(11;14)(p13;q11) and all were classified as poor risk. Patients with any of these translocations had outcomes similar to those with normal diploid karyotypes. CONCLUSION Chromosomal abnormalities, including specific nonrandom translocations, were frequently observed in a large group of children with T-lineage ALL, but were not significant prognostic factors for this cohort. Thus, contemporary intensive treatment programs result in favorable outcomes for the majority of T-lineage ALL patients, regardless of karyotypic abnormalities, and such features do not identify patients at higher risk for relapse.

[1]  H. Sather,et al.  Response of children with high-risk acute lymphoblastic leukemia treated with and without cranial irradiation: a report from the Children's Cancer Group. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  H. Sather,et al.  Clinical features and treatment outcome of childhood T-lineage acute lymphoblastic leukemia according to the apparent maturational stage of T-lineage leukemic blasts: a Children's Cancer Group study. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  H. Adams,et al.  Clinical features and outcome of children with first marrow relapse of acute lymphoblastic leukemia expressing BCR-ABL fusion transcripts. BFM Relapse Study Group. , 1996, Blood.

[4]  H. Seuánez,et al.  Translocation 11;14 in three children with acute lymphoblastic leukemia of T-cell origin. , 1995, Cancer genetics and cytogenetics.

[5]  J. Downing,et al.  Acute lymphoblastic leukemias with deletion of 11q23 or a novel inversion (11)(p13q23) lack MLL gene rearrangements and have favorable clinical features. , 1995, Blood.

[6]  N. Heerema,et al.  Cytogenetic features of infants less than 12 months of age at diagnosis of acute lymphoblastic leukemia: impact of the 11q23 breakpoint on outcome: a report of the Childrens Cancer Group. , 1994, Blood.

[7]  R. Gelber,et al.  Treatment of childhood acute lymphoblastic leukemia: results of Dana-Farber Cancer Institute/Children's Hospital Acute Lymphoblastic Leukemia Consortium Protocol 85-01. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  C. Pui.  Acute leukemias with the t(4;11)(q21;q23). , 1992, Leukemia & lymphoma.

[9]  R. Foà,et al.  Unique genotypic features of infant acute lymphoblastic leukaemia at presentation and at relapse , 1992, British journal of haematology.

[10]  J. Rowley,et al.  The LCK Gene Is Involved in the t(1;7)(p34;q34) in the T‐Cell Acute Lymphoblastic Leukemia Derived Cell Line, HSB‐2 , 1991, Genes, chromosomes & cancer.

[11]  J. Sklar,et al.  TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms , 1991, Cell.

[12]  D. Catovsky,et al.  Inversions and tandem translocations involving chromosome 14q11 and 14q32 in T-prolymphocytic leukemia and T-cell leukemias in patients with ataxia telangiectasia. , 1991, Cancer genetics and cytogenetics.

[13]  F. Behm,et al.  Clinical and biologic features of childhood T-cell leukemia with the t(11;14) , 1991 .

[14]  S. Korsmeyer,et al.  Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukemia. , 1991, Science.

[15]  M. Perutz,et al.  The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[16]  F. Behm,et al.  Improved outcome in childhood acute lymphoblastic leukaemia with reinforced early treatment and rotational combination chemotherapy , 1991, The Lancet.

[17]  A. Bernard,et al.  Comparison of outcome, clinical, laboratory, and immunological features in 164 children and adults with T-ALL. The Groupe d'Etude Immunologique des Leucémies. , 1990, Leukemia.

[18]  C. Pui,et al.  Biology and Clinical Significance of Cytogenetic Abnormalities in Childhood Acute Lymphoblastic Leukemia , 1990 .

[19]  M. Borowitz,et al.  Favorable prognosis associated with hyperdiploidy in children with acute lymphocytic leukemia correlates with extra chromosome 6. A pediatric oncology group study , 1990, Cancer.

[20]  S. Korsmeyer,et al.  The t(10;14)(q24;q11) of T-cell acute lymphoblastic leukemia juxtaposes the delta T-cell receptor with TCL3, a conserved and activated locus at 10q24. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[21]  T. Rabbitts,et al.  The human T cell receptor genes are targets for chromosomal abnormalities in T cell tumors , 1989, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  C. Bloomfield,et al.  Six-year follow-up of the clinical significance of karyotype in acute lymphoblastic leukemia. , 1989, Cancer genetics and cytogenetics.

[23]  S. Korsmeyer,et al.  The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts, including Ttg-1, a gene encoding a potential zinc finger protein , 1989, Molecular and cellular biology.

[24]  B. Koller,et al.  Biphenotypic leukemic lymphocyte precursors in CD2+CD19+ acute lymphoblastic leukemia and their putative normal counterparts in human fetal hematopoietic tissues. , 1989, Blood.

[25]  D. Albertson,et al.  Analysis of a T-cell tumor-specific breakpoint cluster at human chromosome 14q32. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[26]  J. Shuster,et al.  Clinical features and outcome in childhood T-cell leukemia-lymphoma according to stage of thymocyte differentiation: a Pediatric Oncology Group Study. , 1988, Blood.

[27]  H. Sather,et al.  INTENSIVE THERAPY FOR CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKAEMIA AND UNFAVOURABLE PRESENTING FEATURES Early Conclusions of Study CCG-106 by the Childrens Cancer Study Group , 1988, The Lancet.

[28]  P. Nowell,et al.  Molecular analysis of a t(7;14)(g35;g32) chromosome translocation in a T cell leukemia of a patient with ataxia telangiectasia , 1988, Cell.

[29]  T. Rabbitts,et al.  The mechanism of chromosomal translocation t(11;14) involving the T‐cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15. , 1988, The EMBO journal.

[30]  S. Smith,et al.  Chromosomal translocation involving the beta T cell receptor gene in acute leukemia , 1988, The Journal of experimental medicine.

[31]  M. Borowitz,et al.  Immunologic and clinicopathologic features of common acute lymphoblastic leukemia antigen‐positive childhood T‐cell leukemia A pediatric oncology group study , 1987, Cancer.

[32]  R. Gelber,et al.  Four-agent induction and intensive asparaginase therapy for treatment of childhood acute lymphoblastic leukemia. , 1986, The New England journal of medicine.

[33]  A. Look,et al.  Chromosomal translocations play a unique role in influencing prognosis in childhood acute lymphoblastic leukemia. , 1986, Blood.

[34]  A. Bleyer,et al.  Improved disease-free survival of children with acute lymphoblastic leukemia at high risk for early relapse with the New York regimen--a new intensive therapy protocol: a report from the Childrens Cancer Study Group. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  J. Rowley,et al.  Lymphoblastic leukemia with lymphomatous features associated with abnormalities of the short arm of chromosome 9. , 1985, The New England journal of medicine.

[36]  N. Heerema,et al.  Karyotypic and clinical findings in a consecutive series of children with acute lymphocytic leukemia. , 1985, Cancer genetics and cytogenetics.

[37]  C. Pui,et al.  Prognostic importance of blast cell DNA content in childhood acute lymphoblastic leukemia. , 1985, Blood.

[38]  K. Starling,et al.  Modified LSA2-L2 treatment in 53 children with E-rosette-positive T-cell leukemia: results and prognostic factors (a Pediatric Oncology Group Study). , 1982, Blood.

[39]  M. Pike,et al.  Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. , 1977, British Journal of Cancer.

[40]  N. Mantel.  Evaluation of survival data and two new rank order statistics arising in its consideration. , 1966, Cancer chemotherapy reports.

[41]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[42]  C. Pui,et al.  Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  F. Behm,et al.  Heterogeneity of presenting features and their relation to treatment outcome in 120 children with T-cell acute lymphoblastic leukemia. , 1990, Blood.

[44]  J. Pullen,et al.  Clinical and biologic features predict poor prognosis in acute lymphoid leukemias in children and adolescents: a Pediatric Oncology Group review. , 1986, Medical and pediatric oncology.

[45]  G. Henze,et al.  Thymic involvement and initial white blood count in childhood acute lymphoblastic leukemia. , 1981, The American journal of pediatric hematology/oncology.

[46]  Iscn.  International System for Human Cytogenetic Nomenclature , 1978 .