Signal antonymy unique to myelodysplastic marrows correlates with altered expression of E2F1

Suneel D. Mundle, B. Yifwayimare Mativi, Jonathan D. Cartlidge, Bruce Dangerfield, La Tanya Broady-Robinson, Biarou Li, Vilasini Shetty, Parameswaran Venugopal, Stephanie A. Gregory, Harvey D. Preisler, Azra Raza

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Myelodysplastic syndromes (MDS) have previously been reported to show competitively high rates of apoptosis and proliferation in the bone marrow (BM). Using a double-labelling technique in the present study, we demonstrated that a significantly high number of S-phase cells were simultaneously apoptotic (signal antonymy; SA) in MDS (mean ± s.e.m. 53.5 ± 6.7%, n = 24, P < 0.001). In contrast, SA was negligible in all other specimens studied, including normal control BM (n = 13) from non-Hodgkin's lymphoma (NHL) patients, BM from patients with de novo acute myelogenous leukaemia (1'AML; n = 5), or secondary AML that had transformed from MDS (2'AML; n = 10), or the solid tumours from patients with NHL (n = 9) or head and neck squamous cell carcinoma (HNSCC; n = 10). Subsequently, the expression of a transcription factor, E2F1, was studied in density-separated BM aspirate mononuclear cells from MDS patients (n = 9) and a normal control. Two separate sets of primers were used that recognized the regulatory retinoblastoma (Rb) protein-binding region and the functional DNA-binding region of E2F1. Interestingly, although the latter manifested the expected band (280 bp) in all samples, the Rb-specific primers showed the expected band (380 bp) in the normal and in 4/9 MDS specimens. Two other MDS specimens also showed a smaller band (~ 325 bp), whereas 3/9 MDS patients showed exclusively the smaller band. The levels of SA were significantly higher in those MDS cases that showed the smaller Rb-specific band either alone or in addition to the expected band (median 19.5%, n = 4, P = 0.037) than in those showing exclusively the expected band (median 0.4%, n = 3). Our present studies show SA as a characteristic feature of MDS and, importantly, demonstrate its link with an altered expression of E2F1 in some MDS patients.

Original languageEnglish (US)
Pages (from-to)376-381
Number of pages6
JournalBritish Journal of Haematology
Volume109
Issue number2
DOIs
StatePublished - Jun 24 2000
Externally publishedYes

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Keywords

  • Apoptosis
  • DNA synthesis
  • E2F1
  • Myelodysplastic syndromes
  • Signal antonymy

ASJC Scopus subject areas

  • Hematology

Cite this

Mundle, S. D., Mativi, B. Y., Cartlidge, J. D., Dangerfield, B., Broady-Robinson, L. T., Li, B., Shetty, V., Venugopal, P., Gregory, S. A., Preisler, H. D., & Raza, A. (2000). Signal antonymy unique to myelodysplastic marrows correlates with altered expression of E2F1. British Journal of Haematology, 109(2), 376-381. https://doi.org/10.1046/j.1365-2141.2000.01937.x