Characterization of bone marrow stromal abnormalities in a patient with constitutional trisomy 8 mosaicism and myelodysplastic syndrome.
The development of myeloid leukemias and myelodysplastic syndrome (MDS) is common in children with trisomy 8 mosaicism. However, the mechanisms by which the presence of an additional chromosome 8 translates to an increased risk of leukemias and MDS is currently unknown. The authors describe the analysis of stromal cells from a pediatric MDS patient with constitutional trisomy 8. Patient and control marrow stromal cells were analyzed for alterations in cytokine production. Clonogenic assays were used to examine stromal support for hematopoiesis. The interplay between leukemia cells and stroma was studied by co-culture experiments. The results indicate that stromal cell function in this patient was seriously altered in favor of progenitor cell proliferation and expansion. This indicates that constitutional trisomy 8 in stromal cells plays a critical role in the pathogenesis of MDS.
Narendran
Aru
A
Southern Alberta Children's Cancer Program, Alberta Children's Hospital, 1820, Richmond Road SW, Calgary, Alberta T2T 5C7, Canada. a.narendran@ucalgary.ca
Hawkins
Lindsay M
LM
Ganjavi
Hooman
H
Vanek
Wilma
W
Gee
Matthew F
MF
Barlow
Jason W
JW
Johnson
Grant
G
Malkin
David
D
Freedman
Melvin H
MH
D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D002648:Child; D002898:Chromosomes, Human, Pair 8; D018920:Coculture Techniques; D016207:Cytokines / Q000032:analysis; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D009030:Mosaicism; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D017154:Stromal Cells / Q000473:pathology* / Q000502:physiology; D014314:Trisomy; D014407:Tumor Cells, Cultured
D016207:Cytokines