Presence of activation-related m-RNA for EBV and CMV in the bone marrow ofpatients with myelodysplastic syndromes

The bone marrow (BM) in myelodysplastic syndromes (MDS) undergoes pathobiol ogical changes that mimic an inflammatory process, and hence, an infectious etiology was suspected in these disorders. In the present report, we exami ned the bone marrow mononuclear cells (BMMNC) of 19 MDS patients and seven normal donors for the expression of one latency-related (Latency membrane p rotein 1 (LMP-1) and immediate early protein (IEP)) and one activation-rela ted (BZLF and DNA-Pol) mRNA each for two herpes viruses, Epstein-Barr virus (EBV) and cytomegalovirus (CMV), respectively. Reverse transcriptase polym erase chain reaction was used for this purpose. The latency-related transcr ipts (EBV-LMP-1 and CMV-IEP) were present in all the MDS and normal specime ns. Intriguingly, 10/19 MDS specimens (similar to 53%) and 2/7 normal donor s (similar to 28%) were positive for active EBV-BZLF (P = 0.0067), while 2/ 19 MDS specimens (similar to 11%) with 1/7 normal (similar to 14%) showed a ctive CMV-DNA-Pol (P = 0.1588). Later, from another set of MDS patients (n = 7) and normal donors (n = 4), BM stromal cultures were established, which , at a 75% confluency, were overlaid with cord blood mononuclear cells (CBM NC), IEP was detectable in the CBMNC before and after co-incubation with MD S, as well as normal stroma, So, it was also present both in MDS and normal stromal cells. The other three were absent both in MDS and normal stromal layers. In CBMNC though, active EBV-BZLF and CMV-DNA-Pol m-RNA were detecta ble in one of seven MDS co-cultures each, albeit from different patients. N one of the normal co-cultures showed active virus, either in stroma or CBMN C. Thus, the present report demonstrates, for the first time, the presence of active herpes viruses in the BMMNC of MDS patients and reveals the abili ty of the MDS stroma to support the viral activation. (C) 2001 Elsevier Sci ence Ireland Ltd. All rights reserved.