Viral Infections in Juvenile Myelomonocytic Leukemia: Prevalence and Clinical Implications.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
From the *Department of Pediatric Hematology-Oncology, Institute of Medical Science, University of Tokyo, Tokyo; †Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan; ‡Department of Pediatrics, Osaka University, Osaka, Japan; §Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan; ¶Department of Pediatrics, Miyazaki Medical College, Miyazaki, Japan; ∥Department of Pediatrics, Nara Medical University, Nara, Japan; and **Department of Pediatrics, Kyoto University, Kyoto, Japan.
Atsushi
A
Manabe
Tetsu
T
Yoshimasu
Yasuhiro
Y
Ebihara
Hiroshi
H
Yagasaki
Mika
M
Wada
Kumiko
K
Ishikawa
Junichi
J
Hara
Kenichi
K
Koike
Hiroshi
H
Moritake
Yong Dong
YD
Park
Kohichiro
K
Tsuji
Tatsutoshi
T
Nakahata