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Abnormalities of adherent layers grown from bone marrow of patients with myelodysplasia

Tennant, Graham Burt, Walsh, Valerie, Truran, L. N., Edwards, P., Mills, Kenneth Ian and Burnett, Alan Kenneth 2000. Abnormalities of adherent layers grown from bone marrow of patients with myelodysplasia. British Journal of Haematology 111 (3) , pp. 853-862. 10.1111/j.1365-2141.2000.02467.x

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Abstract

Myelodysplastic syndromes (MDS) are characterized by a clonal disorder of haemopoiesis with defective growth in vitro. The long-term culture system was used to examine aspects of stromal function in MDS patients. Primary long-term cultures of MDS bone marrow showed poor myelopoiesis with progenitors being detected for a median 3.5 weeks (n = 12) compared with 18 weeks in cultures of normal marrow (n = 10; P < 0.0001). The haemopoietic function of adherent layers was assessed in secondary co-cultures seeded with 5 x 10(6) cord blood mononuclear cells on irradiated normal (n = 27; aged 38-82 years) or MDS (n = 32; aged 41-86 years) adherent layers (> 60% confluent). The median myeloid progenitor number/cord blood co-culture was 135 in 5-week-old cultures with normal adherent layers and 22 in those with MDS layers (P < 0.0001). Myeloid colonies were detectable for a median 11 weeks with normal adherent layers and 6 weeks with MDS adherent layers (P < 0.0001); erythroid colonies were detectable for 7 weeks (normal) compared with 5 weeks (MDS) (P < 0.01). The differences in granulocyte-macrophage colony forming unit (CFU-GM) generation were not related to patient age. Cells from adherent layers of at least half of the primary normal (n = 48) and MDS (n = 26) long-term cultures expressed cytokines [interleukin (IL)-3, IL-1 beta, thrombopoietin (Tpo) and erythropoietin (Epo)] and receptors for retinoic acid (RAR alpha) [IL-2, IL-3, macrophage colony stimulating factor (M-CSF) (Fms) and Tpo (Mpl)]. Only IL-1 beta expression was reduced in week-5 MDS cultures compared with those from normal marrows (P < 0.05). There was also a highly significant decline in IL-1 beta expression in normal (but not MDS) adherent layers between week 5 and week 10. Thus, the adherent layers in cultures grown from MDS patients were haemopoietically defective and showed abnormal IL-1 beta expression.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: age; erythroid progenitors; interleukin-1β mRNA expression; myeloid progenitors; thrombopoietin
Publisher: Wiley-Blackwell
ISSN: 0007-1048
Last Modified: 31 Jan 2020 05:14
URI: http://orca-mwe.cf.ac.uk/id/eprint/58429

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