A Case of Biclonal Leukemia in a Child Yuichi OGURA,1 Yasuhiko trox,1 Takeshi ASANO,1 Kouzou OHTA, 1 Kiyoshi KANEKO,1 Yoshitaka FUKUNAGA, 1 Masa

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1 A Case of Biclonal Leukemia in a Child Yuichi OGURA,*1 Yasuhiko trox,*1 Takeshi ASANO,*1 Kouzou OHTA, *1 Kiyoshi KANEKO,*1 Yoshitaka FUKUNAGA, *1 Masao YAMAMOTO,*1 Yutaka UEDA,*1 Kozue NAKAMURA*2 and Shuhki MIZUTANI*2 *1 Department of Pediatrics, Nippon Medical School *2 National Children's Medical Research Center Abstract A 10-year-old girl with acute mixed lineage leukemia (AMLL) is presented. Bone marrow examination at diagnosis showed 66.5% small leukemic cells with lymphoblastoid feature and 30.0% large leukemic cells with monocytoid feature. Surface marker analyses revealed that large leukemic cells expressed CD2, CD 19, HLA-DR, CD33, and LeuM3, whereas small leukemic cells bore only CD2 antigen. Both of these leukemic cell populations were negative for periodic acid-schiff, peroxidase, and alpha naphthyl butyrate esterase. Large leukemic cells phagocytized ox red blood cells coated with goat antimouse immunoglobulin antibody, but small leukemic cells did not. These findings were compatible with those of AMLL composed of two separate leukemic cell populations. Additional studies using X-chromosome-linked DNA polymorphism to determine the clonal origin of the leukemic cells supported the idea that these two leukemic cell populations originated from two independent clones in the bone marrow. Thus, recombinant technology is helpful for the study of clonal origin of leukemias with a mixed lineage phenotype. Key words: biclonal leukemia, HPRT, X chromosome linked DNA polymorphism Reprint requests to Yuichi Ogura, Department of Pediatrics, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113 Japan

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3 100 Immunoglobulin gene rearrangements Left lane: patient, right lane: "C" control, pd: partial digest, G: germ line band, : rearrange band } 3 Restriction map of the 5' part of the hypoxanthine phosphoribosyltransferase (HPRT) gene shown with BamHI and HpaII endonuclease restriction (cleavage) sites. The solid bar indicates the region contained in clone ppb1.7 used as hybridization probe. The BamHI endonuclease sites B1 and B3 are present in all X chromosomes, but 16% of X chromosomes contain an additional BamHI site, B2; hence, 27% of females will be heterozygous at the HPRT locus. 9 HpaII sites, H1 to H9, exist between B1 and B2. This enzyme cleaves at the sequence CCGG (C denotes cystone, and G guanine), but does not cleave this sequence when the interna lcystone is methylated. HpaII sites H1 to H3 are usually, but not always, methylated in inactive X chromosomes. HpaII sites H4 to H9 are methylated in over 95% of active X chromosomes, but at least one of sites H4 to H9 is unmethylated in inactive X chromosomes. (Diagram modified from Ref. 2) and 13))

5 2) Vogelstein B, Fearon ER, Hamilton SR, et al : Use of restriction fragment length polymorphisms to determine the clonal origin of human tumors. Science 227: , ) Greaves MF : "Target" cells, cellular phenotypes, and lineage fidelity in human leukaemia. J Cell Physiol 1: , ) Dow IW, Martin P, Moohr J, et al: Evidence for clonal development of childhood acute lymphoblastic leukemia. Blood 66: , ) Mirro J, Zipf TF, Pui CH, et al : Acute mixed lineage leukemia : clinicopathologic correlations and prognostic significance. Blood 66: , ) Stass SA, Mirro J : Lineage heterogeneity in acute leukaemia : Acute mixed-lineage leukemia and lineage switch. Clin Hematol 15: , ) Sobol RE, Mick R, Royston I, et al: Clinical importance of mycloid antigen expression in adult acute lymphoblastic leukemia. N Engl J Med 316: , ) Ludwig WD, Bartram CR, Ritter J, et al: Ambiguous phenotypes and genotypes in 16 children with acute leukemia as characterized by multiparameter analysis. Blood 71: , ) Gale RP, Bassat IB: Annotation Hybrid acute leukemia. Br J Haematol 65: , ) Smith LJ, Curtis JE, Messner HA, et al : Lineage infidelity in acute leukemia. Blood 61: , ) Greaves MF, Chan LC, Furley A JW, et al: Lineage promiscuity in hematopoietic differentiation and leukemia. Blood 67: 1-11, ) Fearon ER, Burke PJ, Schiffer CA, et al: Differentiation of leukemia cells to polymorphonuclear leukocytes in patients with acute nonlymphocytic leukemia. N Engl J Med 315: 15-24, 1986

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