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BCL11A gene over-expression in high risk neuroblastoma

      There is a growing interest in BCL11A (BAF Chromatin Remodelling Complex Subunit) as part of the Locus Controlling Region (LCR) that is responsible for the gamma to beta-globin switch that takes place around the age of 6 months. Children with sickle cell anemia and Beta thalassemia have no manifestation of their disease until they have this switch which exposes their diseased genes. Targeting the erythroid enhancer of BCL11A using CRISPR-Cas9 genome-editing technology showed promise and was recently applied to a patient with sickle cell anemia, leading to fetal hemoglobin production and potentially ameliorating her disease [
      • The Lancet H.
      CRISPR-Cas9 gene editing for patients with haemoglobinopathies.
      ]. A change of behavior during infancy is also pertinent to infantile neuroblastoma. Interestingly, infants with disseminated neuroblastoma who do not have MYCN gene amplification have favorable outcome. These infants undergo a process of spontaneous differentiation and tumor regression, even with no therapeutic intervention [
      • Schwartz A.D.
      • Dadash-Zadeh M.
      • Lee H.
      • Swaney J.J
      Spontaneous regression of disseminated neuroblastoma.
      ]. Of note, metastatic neuroblastoma is the primary cause of cancer-specific mortality in children as the behavior of the disease changes dramatically in children diagnosed after the age of 18-months [
      • London W.B.
      • Castleberry R.P.
      • Matthay K.K.
      • Look A.T.
      • Seeger R.C.
      • Shimada H.
      • Thorner P.
      • Brodeur G.
      • Maris J.M.
      • Reynolds C.P.
      • Cohn S.L
      Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the children's oncology group.
      ]. We asked the question whether BCL11A plays a role in the aggressive behavior in older children with neuroblastoma. In other words, could the expression of this gene in children with metastatic neuroblastoma explain the lack of infantile behavior: volume stabilization and regression?
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