Distinct in Vivo Engraftment and Growth Patterns of t(1;19)⁺/E2A-PBX1⁺ and t(9;22)⁺/BCR-ABL⁺ Human Leukemia Cells in SCID Mice

Barabara J. Waurzyniak Children's Cancer Group ALL Biology Reference Laboratory and Wayne Hughes Institute, St Paul, MN; Group Operations Center, Children's Cancer Group, Arcadia, CA; Department of Pediatric Hematology-Oncology, University of Wisconsin, Madison, WI; Department of Preventive Medicine, University of Southern California, Los Angeles, CA; Department of Hematology-Oncology, Children's National Medical Center, and the George Washington University, Washington, DC, USA

Nyla Heerema Children's Cancer Group ALL Biology Reference Laboratory and Wayne Hughes Institute, St Paul, MN; Group Operations Center, Children's Cancer Group, Arcadia, CA; Department of Pediatric Hematology-Oncology, University of Wisconsin, Madison, WI; Department of Preventive Medicine, University of Southern California, Los Angeles, CA; Department of Hematology-Oncology, Children's National Medical Center, and the George Washington University, Washington, DC, USA

Martha G. Sensel Children's Cancer Group ALL Biology Reference Laboratory and Wayne Hughes Institute, St Paul, MN; Group Operations Center, Children's Cancer Group, Arcadia, CA; Department of Pediatric Hematology-Oncology, University of Wisconsin, Madison, WI; Department of Preventive Medicine, University of Southern California, Los Angeles, CA; Department of Hematology-Oncology, Children's National Medical Center, and the George Washington University, Washington, DC, USA

Paul S. Gaynon Children's Cancer Group ALL Biology Reference Laboratory and Wayne Hughes Institute, St Paul, MN; Group Operations Center, Children's Cancer Group, Arcadia, CA; Department of Pediatric Hematology-Oncology, University of Wisconsin, Madison, WI; Department of Preventive Medicine, University of Southern California, Los Angeles, CA; Department of Hematology-Oncology, Children's National Medical Center, and the George Washington University, Washington, DC, USA

Peter Kraft Children's Cancer Group ALL Biology Reference Laboratory and Wayne Hughes Institute, St Paul, MN; Group Operations Center, Children's Cancer Group, Arcadia, CA; Department of Pediatric Hematology-Oncology, University of Wisconsin, Madison, WI; Department of Preventive Medicine, University of Southern California, Los Angeles, CA; Department of Hematology-Oncology, Children's National Medical Center, and the George Washington University, Washington, DC, USA

Harland N. Sather Children's Cancer Group ALL Biology Reference Laboratory and Wayne Hughes Institute, St Paul, MN; Group Operations Center, Children's Cancer Group, Arcadia, CA; Department of Pediatric Hematology-Oncology, University of Wisconsin, Madison, WI; Department of Preventive Medicine, University of Southern California, Los Angeles, CA; Department of Hematology-Oncology, Children's National Medical Center, and the George Washington University, Washington, DC, USA

Lisa Chelstrom Children's Cancer Group ALL Biology Reference Laboratory and Wayne Hughes Institute, St Paul, MN; Group Operations Center, Children's Cancer Group, Arcadia, CA; Department of Pediatric Hematology-Oncology, University of Wisconsin, Madison, WI; Department of Preventive Medicine, University of Southern California, Los Angeles, CA; Department of Hematology-Oncology, Children's National Medical Center, and the George Washington University, Washington, DC, USA

Gregory H. Reaman Children's Cancer Group ALL Biology Reference Laboratory and Wayne Hughes Institute, St Paul, MN; Group Operations Center, Children's Cancer Group, Arcadia, CA; Department of Pediatric Hematology-Oncology, University of Wisconsin, Madison, WI; Department of Preventive Medicine, University of Southern California, Los Angeles, CA; Department of Hematology-Oncology, Children's National Medical Center, and the George Washington University, Washington, DC, USA

Fatih M. Uckun Children's Cancer Group ALL Biology Reference Laboratory and Wayne Hughes Institute, St Paul, MN; Group Operations Center, Children's Cancer Group, Arcadia, CA; Department of Pediatric Hematology-Oncology, University of Wisconsin, Madison, WI; Department of Preventive Medicine, University of Southern California, Los Angeles, CA; Department of Hematology-Oncology, Children's National Medical Center, and the George Washington University, Washington, DC, USA

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Abstract

The SCID mouse represents a valuable tool for assessing growth characteristics and drug sensitivity of human leukemic cells. We have examined differences in the engraftment patterns in SCID mice of primary human leukemic cells isolated from children (< 21 years old) with either t(1;19)⁺/E2A-PBX1⁺ or t(9;22)⁺/BCR-ABL⁺ acute lymphoblastic leukemia. Leukemic cells from 13/24 t(1;19)⁺/E2A-PBX1⁺ patients caused overt leukemia in SCID mice. Macroscopic lesions were evident in 6/13 cases, with multiple sites involved in some mice: hepatomegaly,(3) splenomegaly(4), thymic enlargement; liver tumors(1), kidney tumors(1), abdominal tumors(1). Microscopic lesions in SCID mouse organs were present in all 13 cases and involved the bone marrow, brain, heart, gut, liver, kidney, lung, ovary, pancreas, skeletal muscle, spleen, and thymus. Leukemic cells from 5/20 t(9;22)⁺/BCR-ABL⁺ patients caused overt leukemia in SCID mice. Notably, macroscopic lesions (splenomegaly; leukemic bones; hepatic tumors) were observed in only 1 case. In all 5 cases, microscopic lesions were found in the mouse bone marrow. Additional microscopic lesions were restricted to skeletal muscle, spleen, and mesentery (1 case) or thymus (1 case). These findings differ markedly from those of t(1;19)⁺/E2A-PBX1⁺ leukemic cells due to the lack of involvement of major organs such as liver, pancreas, kidney, skin, or brain. These data illustrate the biological heterogeneity of childhood ALL and suggest that the differential risks associated with t(1;19)⁺/E2A-PBX1⁺ and t(9;22)⁺/BCR-ABL ALL might arise from unique engraftment and proliferation capabilities of the respective leukemic cell populations.

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Distinct in Vivo Engraftment and Growth Patterns of t(1;19)⁺/E2A-PBX1⁺ and t(9;22)⁺/BCR-ABL⁺ Human Leukemia Cells in SCID Mice

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Distinct in Vivo Engraftment and Growth Patterns of t(1;19)+/E2A-PBX1+ and t(9;22)+/BCR-ABL+ Human Leukemia Cells in SCID Mice

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Distinct in Vivo Engraftment and Growth Patterns of t(1;19)⁺/E2A-PBX1⁺ and t(9;22)⁺/BCR-ABL⁺ Human Leukemia Cells in SCID Mice