Objectives: Viral infections
may complicate the diagnosis of juvenile myelomonocytic leukemia
(JMML) in a substantial proportion of patients, but this possibility has not been tested in a prospective study. The authors therefore measured the cellular expression of the MxA
protein, a reliable marker of viral infection, at diagnosis in children with JMML to estimate the prevalence of such infections.
Eighteen children, aged 1 to 69 months, who met the diagnostic criteria of the International JMML Working Group were prospectively studied. MxA
expression was assessed by flow cytometric analysis of peripheral blood mononuclear cells stained with an antihuman MxA
antibody. All data were obtained through the MDS Committee of the Japanese Society of Pediatric Hematology.
Twelve patients (67%) had elevated levels of the MxA
protein, with rotavirus, RS virus, or CMV infection documented in three of these patients. Although none of the patients had primary Epstein-Barr virus
(EBV) infection, reactivation of the virus was strongly suspected in four children, including two with monosomy 7
, each having increased levels of MxA
. Southern blot analysis revealed monoclonal integration of the EBV genome into bone marrow mononuclear cells from one of these patients. There was no discernible correlation between increases in the marker protein and the presenting features or course of the disease.
Viral infection may be present in two thirds of children with newly diagnosed JMML, but it does not constitute a basis for revising clinical management. The possibility that EBV or other viruses contribute to JMML pathogenesis by stimulating pre-exiting malignant clones warrants further investigation.