Summary
Secondary acute myeloid leukemia occurring in a 15-year-old boy 11 years after initial treatment of a common lymphoblastic leukemia (c-ALL) is described. Initial complete remission was terminated after 4 years by an isolated testicular relapse, followed by first bone marrow relapse within 18 months. After he achieved remission again, an allogeneic bone marrow transplantation from his HLA-identical brother was performed. Five years and 9 months later, the patient developed thrombocytopenia, leukopenia, and anemia, but bone marrow biopsies at this time demonstrated only myelofibrosis, with no blast cell population present. A polymerase chain reaction assay of a peripheral blood sample recognized the mRNA fusion region for the MLL/AF4 rearrangement, i.e., the molecular equivalent of the translocation (4;11)(q21,q23). Four weeks later, a blast cell population with AML-M1 morphology according to the FAB classification appeared in the bone marrow, and translocation (4;11) was detected by cytogenetics. Thus, secondary leukemias with chromosomal 11q23 rearrangement can develop after a long latency period and can be diagnosed earlier with the PCR technique.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bernard OA, Mauchauffe M, Mecucci C, Van den Berghe H, Berger R (1994) A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 or ENL. Oncogene 9:1039–1045
Borkhardt A, Repp R, Haupt E, Brettreich S, Buchen U, Gossen R, Lampert F (1994) Molecular analysis of MLL-1/AF4 recombination in infant acute lymphoblastic leukemia. Leukemia 8:549–553
Chromczynski P, Sacchi N (1987) Single-step method of RNA isolation by guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159
Corral J, Forster A, Thompson S, Lampert F, Kaneko Y, Slater R, van der Schoot CE, Ludwig WD, Pocock C, Cotter F, Rabbitts TH (1993) Acute leukaemias of different lineages have similar MLL gene fusions encoding related chimeric proteins resulting from chromosomal translocation. Proc Natl Acad Sci USA 90:8538–8542
Gu Y, Cimino G, Alder H, Nakamura T, Prasad R, Canaani O, Moir DT, Jones C, Nowell PC, Croce CM, Canaani E (1992) The (4;11)(q21;q23) chromosome translocations in acute leukemias involve the VDJ recombinase. Proc Natl Acad Sci USA 89:10464–10468
Gutjahr P (1990) Das Risiko zweiter bösartiger Neubildungen nach erfolgreicher onkologischer Behandlung im Kindesalter. Padiatr Prax 40:213–226
Henze G, Fengler R, Hartmann R, Niethammer D, Schellong G, Riehm H (1990) BFM group treatment results in relapsed childhood acute lymphoblastic leukemia. Haematol Blood Transfus 33:619–626
Hunger SP, Sklar J, Link MP (1992) Acute lymphoblastic leukemia occurring as a second malignant neoplasm in childhood: report of three cases and review of the literature. J Clin Oncol 10:156
Lampert F, Harbott J, Ludwig WD, Bartram CR, Ritter J, Gerein V, Neidhardt M, Mertens R, Graf N, Riehm H (1987) Acute leukemia with chromosome translocation (4;11): 7 new patients and analysis of 71 cases. Blut 54:325–335
Larson RA, Le Beau MM, Ratain MJ, Rowley JD (1992) Balanced translocations involving chromosome bands 11q23 and 21q22 in therapy-related leukemia. Blood 79:1892–1893
Lennard A, Jackson GH, Carey PJ, Bown N, Middleton P, Proctor SJ (1991) Secondary acute lymphoblastic leukaemia with 4;11 translocation following treatment for Hodgkin's disease: case report and review of the literature. Leukemia 5:624–627
Nakamura T, Alder H, Gu Y, Prasad R, Canaani O, Kamada N, Gale RP, Lange B, Crist WM, Nowell PC, Croce CM, Canaani E (1993) Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs. Proc Natl Acad Sci USA 90:4631–4635
Pedersen-Bjergaard J, Daugaard G, Hansen SW, Philip P, Larsen SO, Rorth M (1991) Increased risk of myelodysplasia and leukemia after etoposide, cisplatin and bleomycin for germ cell tumors. Lancet 338:359
Pedersen-Bjergaard J, Philip P (1991) Balanced translocations involving chromosome bands 11q23 and 21q22 are highly characteristic of myelodysplasia and leukemia following therapy with cytostatic agents targeting at DNA-topoisomerase II. Blood 78:1147–1148
Pedersen-Bjergaard J, Philip P, Larsen SO, Jensen G, Byrsting K (1990) Chromosome aberrations and prognostic factors in therapy-related myelodysplasia and acute nonlymphocytic leukemia. Blood 76:1083–1091
Pedersen-Bjergaard J, Sigsgaard TC, Nielsen D, Gjedde SB, Philip P, Hansen M, Larsen SO, Rorth M, Mouridsen H, Dombernowsky P (1992) Acute monocytic or myelomonocytic leukemia with balanced chromosome translocation to band 11q23 after therapy with 4-epi-doxorubicin and cisplatin or cyclophosphamide for breast cancer. J Clin Oncol 10:1444–1451
Prasad R, Gu Y, Alder H, Nakamura T, Canaani O, Saito H, Huebner K, Gale RP, Nowell PC, Kuriyama K, Miyazaki Y, Croce CM, Canaani E (1993) Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with t(6;11) chromosome translocation. Cancer Res 53:5624–5628
Prieto F, Palau F, Badia L, Beneyto M, Perez-Sirvent ML, Orts A, Castel V (1990) 11q23 abnormalities in children with acute nonlymphocytic leukemia (M4-M5). Association with previous chemotherapy. Cancer Genet Cytogenet 45:1–11
Pui C-H, Behm FG, Raimondi SC, Dodge RK, George SL, Rivera GK, Mirro J, Jr., Kalwinsky DK, Dahl GV, Murphy SB, Crist WM, Williams DL (1989) Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia. N Engl J Med 321:136–142
Pui C-H, Ribeiro RC, Hancock ML, Rivera GK, Evans WE, Raimondi SC, Head DR, Behm FG, Hazem Mahmoud M, Sandlund JT, Crist WM (1991) Acute myeloid leukemia in children treated with epipodophyllotoxins for acute lymphoblastic leukemia. N Engl J Med 325:1682–1687
Pui CH (1992) Acute leukemias with the t(4;11)(q21;q23). Leuk Lymphoma 7:173–179
Reynolds TR, Uliana SRB, Floeter-Winter LM, Buck GA (1993) Optimization of coupled PCR amplification and cycle sequencing of cloned and genomic DNA. Biotechniques 15:462–467
Rubin CM, Arthur DC, Woods WG, Lange BJ, Nowell PC, Rowley JD, Nachman J, Bostrom B, Baum ES, Suarez CR, Shah NR, Morgan E, Maurer HS, McKenzie SE, Larson RA, Le Beau MM (1991) Therapy-related myelodysplastic syndrome and acute myeloid leukemia in children: correlation between chromosomal abnormalities and prior therapy. Blood 78:2982–2988
Sambrock J, Fritch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor University Press, Cold Spring Harbor, NY
Schrappe M, Beck J, Brandeis WE, Feickert H-J, Gadner H, Graf N, Havers W, Henze G, Jobke A, Kornhuber B, Kühl J, Lampert F, Müller-Weihrich St, Niethammer D, Reiter A, Rister M, Ritter J, Schellong G, Tausch W, Weinel P, Riehm H (1987) Die Behandlung der akuten lymphoblastischen Leukämie im Kindes- und Jugendalter: Ergebnisse der multizentrischen Therapiestudie ALL-BFM 81. Klin Padiatr 199:133–150
Thirman MJ, Gill HJ, Burnett RC, Mbangkollo D, McCabe NR, Kobayashi H, Ziemin-van der Poel S, Kaneko Y, Morgan R, Sandberg AA, Chaganti RSK, Larson RA, Le Beau MM, Diaz MO, Rowley JD (1993) Rearrangements of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. N Engl J Med 329:909–914
Wang JC, Caron PR, Kim RA (1990) The role of DNA topoisomerases in recombination and genome stability: a doubleedged sword? Cell 62:403–406
Zaccaria A, Alimena G, Baccarani M, Billström R, Carbonell F, Castoldi GL, Fuscaldo K, Hecht F, Hossfeld DK, Mitelman F, Rosti G, Sandberg AA, Tassinari A, Testoni N, Tura S (1987) Cytogenetic analyses in 89 patients with secondary hematologic disorders — results of a cooperative study. Cancer Genet Cytogenet 26:65–74
Ziemin-van der Poel S, McCabe NR, Gill HJ, Espinosa R, III, Patel Y, Harden A, Rubinelli P, Smith SD, LeBeau MM, Rowley JD, Diaz MO (1991) Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci USA 88:10735–10739
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Blütters-Sawatzki, R., Borkhardt, A., Grathwohl, J. et al. Secondary acute myeloid leukemia with translocation (4;11) and MLL/AF4 rearrangement in a 15-year-old boy treated for common acute lymphoblastic leukemia 11 years earlier. Ann Hematol 70, 31–35 (1995). https://doi.org/10.1007/BF01715379
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01715379