Engraftment of NOD/SCID/gammac(null) mice with multilineage neoplastic cells from patients with juvenile myelomonocytic leukaemia.
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/gammac(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.
Department of Paediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yoichi
Y
Nakamura
Masafumi
M
Ito
Tomoko
T
Yamamoto
Xu Y
XY
Yan
Hiroshi
H
Yagasaki
Yoshiro
Y
Kamachi
Kazuko
K
Kudo
Seiji
S
Kojima
D000818:Animals; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D053631:Interleukin Receptor Common gamma Subunit; D015479:Leukemia, Myelomonocytic, Acute / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D023421:Models, Animal; D009368:Neoplasm Transplantation; D020395:Receptors, Interleukin-7 / Q000235:genetics; D014183:Transplantation, Heterologous
C507941:IL2RG protein, human; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D020395:Receptors, Interleukin-7