The induction of CD10 on a pre-B leukemia cell line occurs with progression of the disease in scid mice.
We have previously demonstrated the engraftment and dissemination of human pre-B acute lymphoblastic leukemia (ALL) cells into scid mice. In the current study, the temporal pattern of infiltration of a CD10- pre-B leukemia line (G2) in various murine tissues and the progression of the disease in the whole animal were monitored by quantifying human CD44 mRNA expression by the polymerase chain reaction (PCR). Irradiated scid mice were injected intravenously with 10(6) G2 cells and killed 3 days to 10 weeks later. After 2 weeks, leukemic cells were found mostly in bone marrow, but also in lung. At 6 to 7 weeks, spleen and lung contained 30% human RNA, while peripheral blood, liver, and kidney contained 2-3%. Infiltration to brain and thymus was observed at 8-9 weeks. In terms of the whole animal, spleen and liver were the major sites of tumor burden. The induction of CD10 expression was previously observed in transplanted CD10- G2 leukemic cells recovered from scid thymus at 10-12 weeks, which corresponds to the terminal stage of disease. In this study, the CD10 expression on the leukemic cells was monitored at earlier time points by flow cytometry and quantitative PCR. Induction of CD10 was first observed in bone marrow, spleen, peripheral blood, and liver at 6-7 weeks (10-fold), at the time of the onset of dissemination of the leukemia. Despite the presence of 30% human RNA in lung at 6-7 weeks, CD10 induction was not significant in that site before 10 weeks. Increased levels of CD10 were seen in all tissues between 8 and 10 weeks; the highest levels were observed in leukemic cells proliferating in thymus (113-fold) and in those found in circulation. These findings suggest that initial induction of CD10 occurs in hematopoietic tissues at the time of rapid proliferation of the leukemic cells and their infiltration of several tissues. At later time points, the increase in CD10 expression is seen on the leukemic cells found in all peripheral organs suggesting an association with disease progression.
Ishii
E
E
Division of Immunology/Cancer Research, Hospital for Sick Children, Toronto, Canada.
Greaves
A
A
Grunberger
T
T
Freedman
M H
MH
Letarte
M
M
D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors; D017254:Leukemic Infiltration; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D015260:Neprilysin / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000235:genetics; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing; D015260:Neprilysin