Abstract
To increase our knowledge of the clonal relationship of leukaemia relapse, the genotypes and phenotypes of ten children with acute lymphoblastic leukaemia (ALL) were examined at initial diagnosis and relapse. Seven patients were phenotyped as common ALL, two as mixed, and one as T-cell ALL (T-ALL). Comparative analyses of immunoglobulin (Ig) heavy and light chain as well as T-cell receptor β-chain (Tβ) sequences revealed clonal variations, i.e. appearance of a novel or an evoluted leukaemic cell clone in five patients coinciding with the loss of common acute lymphoblastic leukaemic antigen (CALLA) in four cases, irrespective of early or late relapse. Conversion of early B- to T-ALL or lymphoblastic to non-lymphoblastic leukaemia was not noted in any of the patients examined. Our results suggest that clonal variation is a frequent event in childhood ALL.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- Kb:
-
kilobase pairs
- ALL:
-
acute lymphoblastic leukaemia
- CALLA:
-
common acute lymphoblastic leukaemia antigen
- Ig:
-
immunoglobulin
- TCR:
-
T-cell receptor
- Tβ:
-
T-cell receptor β-chain
- FAB:
-
French-American-British
- TdT:
-
terminal deoxynucleotidyl transferase
- T-ALL:
-
T-cell ALL
References
Arnold A, Cossman G, Bakashi A, Jaffe ES, Waldmann TA, Korsmeyer SF (1983) Immunoglobulin gene rearrangements as unique clonal markers in human lymphoid neoplasms. N Engl J Med 309:1593–1598
Bakhshi A, Minovada G, Arnold A, Cossman G, Jensen GP, Whang-Peng G, Waldmann TA, Korsmeyer SF (1983) Lymphoid blast crises of chronic mylogenous leukemia represent stages in the development of B-cell precursors. N Engl J Med 309:826–830
Bennett GM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C (1976) Proposals for the classification of acute leukemias. French-American-British (FAB) Cooperative Group. Br J Haematol 33:451–458
Bollum FJ (1979) Terminal deoxynucleotidyl transferase as a hematopoietic cell marker. Blood 54:1203–1215
Borella L, Casper JT, Lauer ST (1979) Shifts in expression of cell membrane phenotypes in childhood lymphoid malignancies at relapse. Blood 54:64–71
Dow CW, Martin P, Mooler F, Greenberg M, Macdougale CG, Naifeld V, Fialkow PF (1985) Evidence for clonal development of childhood acute lymphoblastic leukemia. Blood 66:902–907
Fialkow PF, Klein E, Klein G, Clifford P, Singh S (1973) Immunoglobulin and glucose-6-phosphate dehydrogenase as markers of cellular origin in Burkitt lymphoma. J Exp Med 138:89–102
Flug F, Pelicci PG, Bonetti F, Knowles DM, Dalla-Favera R (1985) T-cell receptor gene rearrangements as markers of lineage and clonality in T-cell neoplasms. Proc Natl Acad Sci USA 82: 3460–3464
Greaves M, Paxton A, Janossy G, Pain C, Johnsson S, Lister TA (1980) Acute lymphoblastic leukaemia associated antigen. III Alterations in expression during treatment and in relapse. Leuk Res 4:1–14
Hiddemann W, Ludwig WD, Herrmann F, Harbott J, Beck JD, Lampert F, Odenwald E, Riehm H (1986) New techniques in the diagnosis and pretherapeutic characterization of acute leukemias in children: analyses by flow cytometry, immunology and cytogenetics in BFM studies. Monogr Paediatr 18:106–127
Lauer S, Piaskowski V, Camitta B, Casper J (1982) Bone marrow and extramedullary variations of cell membrane antigen expression in childhood lymphoid neoplasias at relapse. Leuk Res 6: 769–774
Pui CH, Raimondi SC, Behm FG, Ochs J, Furman WL, Bunin NJ, Ribeiro RC, Tinsley PA, Mirro J (1986) Shifts in blast cell phenotype and karyotype at relapse of childhood lymphoblastic leukemia. Blood 68:1306–1310
Raghavachar A, Bartram CR, Ganser A, Heil G, Kleihauer E, Kubanek B (1986) Acute undifferentiated leukemia (AUL): implications for cellular origin and clonality suggested by analysis of surface markers and immunoglobulin gene rearrangement. Blood 68:658–661
Rivera GK, Buchanan G, Boyett JM, Camitta B, Ochs J, Kalwinsky D, Amylon M, Vietti TJ, Crist WM (1986) Intensive retreatment of childhood acute lymphoblastic leukemia in first bone marrow relapse. A Pediatric Oncology Group Study. N Engl J Med 315:273–278
Ziegler JL, Bluming AZ, Fass L, Morrow RH (1972) Relapse patterns in Burkitt's lymphoma. Cancer Res 32:1267–1273
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Raghavachar, A., Ludwig, W.D. & Bartram, C.R. Clonal variation in childhood acute lymphoblastic leukaemia at early and late relapse detected by analyses of phenotype and genotype. Eur J Pediatr 147, 503–507 (1988). https://doi.org/10.1007/BF00441975
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00441975