Objective: Acute lymphoblastic leukemia (ALL) is the most common type of cancer in childhood but its etiology is largely unexplained. Epstein Barr Virus (EBV) may play a role in the pathogenesis of ALL by integrating into the genome of precursor B cells, disturbing differentiation and proliferation control.
Case report: Two and a half year old boy admitted with fever. Physical examination findings were unremarkable. Laboratory investigations revealed a low hemoglobin level (9.7g/dL), a low platelet count (31,000cells/mm3), a normal leukocyte count (7130cells/mm3) and also an elevated lactate dehydrogenase level (661U/L). A peripheral blood (PB) examination revealed the presence of leukemic blasts of uncertain origin (51%). A bone marrow (BM) smear showed almost complete infiltration of L1 blasts (94%). Immunophenotyping was consistent with pre-B ALL. Conventional cytogenetic analysis of BM blasts revealed a mosaic karyotype with hypodiploidy (46,XY[7]/45,XY[3]/40-44,XY[2]). FISH analyses showed inversion 16 (20%), trisomy 7(12%). FISH analyses also detected elevated signals suggesting duplications or trisomies at IGH region of 14th chromosome, at ETV6 region of 12th chromosome and at AFF1 region of 4th chromosome. Before chemotherapy EBV DNA was 1563IU/mL in PB. EBV viral capsid antigen (VCA) immunoglobulin (Ig) M was positive and EBV VCA Ig G was low suggesting a primary acute infection. At the end of induction the patient was in remission and EBV DNA could not be detected neither in BM nor in PB. Karyotype and FISH analyses were both normal. Maintenance treatment is going on without an EBV activation.
Methodology: Herein, we present a child with ALL who has EBV positivity and multiple chromosomal abnormalities.
Results: Since EBV was identified, it has been associated with a variety of diseases of hematological origin such as Burkitt's lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disease, hemophagocytic lymphohistiocytosis (HLH) and etc. The same cell type in lymphoma and lymphocytic leukemia lead similar diseases with different clinical manifestations and stages sharing similar biological characteristics. It is reported that lymphocyte chromosome mutations or translocations caused by EBV infection can lead to oncogene activation resulting in the occurrence of lymphoma. In addition, chromosome abnormalities have been observed in EBV-associated HLH and chronic active EBV infection. Ahmed at al. screened 80 pediatric patients with leukemia and 20 healthy controls from Sudan, for the presence of EBV latent membrane protein 1 (LMP1) gene transcripts. Although there was no positivity in the control group, they found high ratios in leukemia group suggesting the role EBV in the etiology of pediatric leukemia. Guan et al. detected EBV DNA copies in BM of both pediatric and adult patients with ALL, AML and they also found higher ratios from healthy controls.
Conclusion: The child we presented herein has pre-B ALL with multiple chromosomal abnormalities detected by karyotype analysis combined with FISH. These anomalies and leukemia itself can be associated with active EBV infection. Studies with large sample sizes to elucidate the possible role of EBV infection in acute leukemias and associated chromosome aberrations are required.
