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Engraftment of NOD/SCID/ γ c null mice with multilineage neoplastic cells from patients with juvenile myelomonocytic leukaemia
Author(s) -
Nakamura Yoichi,
Ito Masafumi,
Yamamoto Tomoko,
Yan Xu Y.,
Yagasaki Hiroshi,
Kamachi Yoshiro,
Kudo Kazuko,
Kojima Seiji
Publication year - 2005
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05578.x
Subject(s) - biology , juvenile myelomonocytic leukemia , haematopoiesis , bone marrow , myeloid , cd3 , stem cell , immunology , cd19 , cancer research , microbiology and biotechnology , cd8 , antigen
Summary 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/ γ c null 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.