Quantitation of human herpes virus 6 genome in children with acute lymphoblastic leukemia

Abstract

Acute lymphoblastic leukemia is the main type of leukemia in children. An infectious etiology has been suspected and the role of the Human herpesvirus-6 (HHV-6) has been suggested. Several studies have tried to establish a link between HHV-6 infections and hematological malignancies, with discordant results. The potential role of HHV-6 in the pathogenesis of pediatric acute lymphoblastic leukemia was investigated. HHV-6 genome copy number was measured by quantitative real-time PCR (RQ-PCR) in bone marrow or peripheral blood samples obtained from 36 children (median age = 4 years) with B acute lymphoblastic leukemia (n = 31) and T acute lymphoblastic leukemia (n = 5) at diagnosis and during complete remission. Positive samples were further characterized to define viral variant, A or B. A total of 24.7% of samples were positive for HHV-6 genome: 13.9% were leukemia samples and 34.1% were complete remission samples. Viral load was low with values lower at diagnosis (median viral copy number = 22.9) than at complete remission (median copy number = 60.1). Among the 17 patients with positive samples, 15 were typed as B-variant whereas 2 could not be typed. These results argue against a role of HHV6 infection in the development of pediatric acute lymphoblastic leukemia. They also suggest that HHV-6 may infect latently bone marrow progenitors but seems not able to infect leukemic cells, raising again the question of the mechanism of virus fusion and entry. This observation shows that a reactivation may be observed during complete remission supporting the possibility of virus reactivation in immunocompromised hosts.

Quantitative analysis of human herpesvirus-6 genome in blood and bone marrow samples from Tunisian patients with acute leukemia: a follow-up study

“…In the bone marrow samples at diagnosis, the current results are in accordance with previous findings obtained by Seror et al who detected HHV-6 in 17% of bone marrow samples with a viral load at 23 copies/million cells [14]. …”

“…[14], but differs from those obtained by Hermouet et al who identified 89% of HHV-6A species, and 11% of HHV-6B [12]. This may be linked to the high number of children included in our study, the frequent occurrence of HHV-6 infections during childhood and to inter-laboratory technical discrepancies.…”

“…At remission, HHV-6 was significantly more prevalent in blood and bone marrow than at diagnosis, confirming the high frequency detection of HHV-6 in patients at remission [14]. …”

“…The median viral loads were at 1,512 copies/million cells for patients with lymphoproliferative disorders [11] and at 1,374 copies/million cells for patients with B-cell malignancies [12]. On the contrary, HHV-6 was similarly detected in patients with acute lymphoblastic leukemia and controls [13], and the virus was more present in children with acute lymphoblastic leukemia at complete remission than at diagnosis [14]. …”

Frequency of Chromosomally-Integrated Human Herpesvirus 6 in Children with Acute Lymphoblastic Leukemia

“…Eight carried HHV-6B and 1 HHV-6A (one could not be not determined). The detection of low HHV-6 viral loads in a small proportion of ALL patients has been observed previously [40], [41]. Of these 11 samples, one (P451) had a HHV-6 copy number consistent with ciHHV-6.…”