Qualitative and quantitative analysis of human herpesviruses in chronic and acute B cell lymphocytic leukemia and in multiple myeloma.
Real-time quantitative polymerase chain reaction (qPCR) was used to quantify viral loads of human herpesviruses (HHVs) at diagnosis in 61 samples of malignant B cells: 21 chronic lymphocytic leukemia (B-CLL), 29 acute lymphoblastic leukemia (B-ALL) and 11 multiple myeloma (MM); control samples were blasts from 16 acute myeloid leukemia (AML) and 24 blood or bone marrow samples from healthy donors. The majority of samples from healthy donors and patients (B-ALL, B-CLL or AML, but not MM) was positive for EBV and contained <100 ebv copies/100 ng dna. ebv loads were occasionally high (>500 copies/100 ng DNA) in B-ALL (2/16) and in B-CLL (2/21) samples. The fractions of samples positive for HHV-8 and HHV-6A, less than 10% for MM patients, were high for adults with B-ALL (18.8% HHV-8+, 43.8% HHV-6A+) or B-CLL (28.6% HHV-8+, 52.4% HHV-6A+). B-ALL, B-CLL and MM samples were rarely positive for HHV-6B and HHV-7. Lastly, 75% of B-ALL samples were positive for CMV, and CMV loads were significantly higher in B-ALL samples than in MM, B-CLL or AML samples. We also used PCR with consensus-degenerate hybrid oligonucleotide primers (CODEHOP) to look for novel HHVs in B cell samples: no sequence indicative of a new HHV was detected. Altogether, the data indicate that the presence of multiple HHVs, including EBV and CMV at high loads, is not rare in B-ALL and B-CLL cell samples. Future prospective studies should determine whether patients with high EBV/CMV loads at diagnosis in tumor samples face a higher risk of delayed hematological recovery, virus-related complications or relapse.
Hermouet
S
S
Department of Microbiology and Immunology, Cornell University, Ithaca, NY, USA.
Sutton
C A
CA
Rose
T M
TM
Greenblatt
R J
RJ
Corre
I
I
Garand
R
R
Neves
A M
AM
Bataille
R
R
Casey
J W
JW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000821:virology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000302:isolation & purification*; D016199:Herpesvirus 7, Human / Q000235:genetics / Q000302:isolation & purification*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000821:virology*; D016133:Polymerase Chain Reaction / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D012680:Sensitivity and Specificity; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D019562:Viral Load
D017931:DNA Primers; D004279:DNA, Viral