Normal and chronic phase CML hematopoietic cells repopulate NOD/SCID bone marrow with different kinetics and cell lineage representation.
BACKGROUND
Chronic myelogenous leukemia is characterized by a clonal expansion of abnormal hematopoietic cells, which eventually replaces normal hematopoiesis. We wanted to test the hypothesis that the growth kinetics of CML and normal hematopoietic cells are different.


METHODS
We compared the growth kinetics and the phenotype of engraftment of chronic phase CML and normal human CD34(+) precursor cells in the bone marrow of immune deficient mice.


RESULTS
High levels of engraftment of normal precursors occurred early and consisted of myeloid, erythroid, megakaryocytic, and lymphoid elements. This level and pattern of engraftment were maintained at later assessments. The level of CML cell engraftment was initially much lower, but it increased progressively at late time-points with no indication of a plateau in growth. Early engraftment of CML cells consisted almost entirely of myeloid and mast cells but soon after only mast cells were detectable. Conversely mast cells were infrequent in mice engrafted with normal progenitors.


CONCLUSIONS
We conclude that in contrast to normal cell engraftment, engraftment of CML cells in NOD/SCID mice is characterized by a slow but progressive myeloid infiltration, which eventually consists almost entirely of mast cells.
Dazzi
F
F
Department of Haematology, Imperial College School of Medicine at Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. f.dazzi@ic.ac.uk
Hasserjian
R
R
Gordon
M Y
MY
Boecklin
F
F
Cotter
F
F
Corbo
M
M
Capelli
D
D
Goldman
J M
JM
D000818:Animals; D002453:Cell Cycle; D019070:Cell Lineage; D006085:Graft Survival; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000473:pathology*; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000637:transplantation*; D011828:Radiation Chimera; D013047:Specific Pathogen-Free Organisms; D014183:Transplantation, Heterologous