Engraftment of NOD/SCID/γcnull mice with multilineage neoplastic cells from patients with juvenile myelomonocytic leukaemia

Yoichi Nakamura, Masafumi Ito, Tomoko Yamamoto, Xu Y. Yan, Hiroshi Yagasaki, Yoshiro Kamachi, Kazuko Kudo, Seiji Kojima

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Several lines of evidence indicate the clonal nature of juvenile myelomonocytic leukaemia (JMML), involving myeloid, erythroid, megakaryocyte and B-lymphoid lineages. However, it is unclear whether the T-lymphocyte lineage is involved. We demonstrated that cells from six patients with JMML repopulated in non-obese diabetic/severe combined immunodeficient/γcnull mice and differentiated into granulocytes, monocytes, erythrocytes, B lymphocytes, T lymphocytes and natural killer cells. The percentage of human CD45 antigen-positive cells ranged from 41% to 73% in the murine bone marrow 12 weeks after transplantation. To examine the involvement of lymphocyte subpopulations, we purified human CD3+, CD19+ and CD56+ cells from murine bone marrow cells transplanted from a patient with monosomy 7. Fluorescence in situ hybridization (FISH) showed the clonal marker in 96-100% of purified CD3+, CD19+ and CD56+ subpopulations. These findings support the concept that JMML originates in transplantable multilineage haematopoietic stem cells. This novel murine xenotransplant model should be useful for investigating the nature of stem cells and testing new therapies for patients with JMML.

Original languageEnglish
Pages (from-to)51-57
Number of pages7
JournalBritish Journal of Haematology
Volume130
Issue number1
DOIs
Publication statusPublished - 01-07-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology

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