title: Presence of activation-related m-RNA for EBV and CMV in the bone marrow of patients with myelodysplastic syndromes.
abstract: The bone marrow (BM) in myelodysplastic syndromes (MDS) undergoes pathobiological changes that mimic an inflammatory process, and hence, an infectious etiology was suspected in these disorders. In the present report, we examined the bone marrow mononuclear cells (BMMNC) of 19 MDS patients and seven normal donors for the expression of one latency-related (Latency membrane protein 1 (LMP-1) and immediate early protein (IEP)) and one activation-related (BZLF and DNA-Pol) m-RNA each for two herpes viruses, Epstein-Barr virus (EBV) and cytomegalovirus (CMV), respectively. Reverse transcriptase polymerase chain reaction was used for this purpose. The latency-related transcripts (EBV-LMP-1 and CMV-IEP) were present in all the MDS and normal specimens. Intriguingly, 10/19 MDS specimens ( approximately 53%) and 2/7 normal donors ( approximately 28%) were positive for active EBV-BZLF (P=0.0067), while 2/19 MDS specimens ( approximately 11%) with 1/7 normal ( approximately 14%) showed active 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 (CBMNC). IEP was detectable in the CBMNC before and after co-incubation with MDS, 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 detectable in one of seven MDS co-cultures each, albeit from different patients. None of the normal co-cultures showed active virus, either in stroma or CBMNC. Thus, the present report demonstrates, for the first time, the presence of active herpes viruses in the BMMNC of MDS patients and reveals the ability of the MDS stroma to support the viral activation.
authors.affiliation: Rush Cancer Institute, Rush-Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA. smundle@rush.edu
authors.forename: S
authors.initials: S
authors.lastname: Mundle
authors.forename: K
authors.initials: K
authors.lastname: Allampallam
authors.forename: K
authors.initials: K
authors.lastname: Aftab Rashid
authors.forename: B
authors.initials: B
authors.lastname: Dangerfield
authors.forename: J
authors.initials: J
authors.lastname: Cartlidge
authors.forename: D
authors.initials: D
authors.lastname: Zeitler
authors.forename: E
authors.initials: E
authors.lastname: Afenya
authors.forename: S
authors.initials: S
authors.lastname: Alvi
authors.forename: V
authors.initials: V
authors.lastname: Shetty
authors.forename: P
authors.initials: P
authors.lastname: Venugopal
authors.forename: A
authors.initials: A
authors.lastname: Raza
mesh_terms: D001853:Bone Marrow / Q000378:metabolism*; D003587:Cytomegalovirus / Q000378:metabolism*; D005312:Fetal Blood / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism; D014775:Virus Activation
chemical_list: D012333:RNA, Messenger