Acute lymphoblastic leukemia in a patient with fragile X syndrome: cytogenetic and molecular features

Malignancies in patients with fragile X syndrome are rarely reported. A 42-year-old man with fragile X syndrome presented with precursor B-cell acute lymphoblastic leukemia (ALL). Cytogenetic analysis showed a stemline 46, XY,t(9;22)(q34;qll) and a sideline 46,XY, t(8;14)(q24;qll), t(9;22)(q34;qll). Molecular analysis of the FMR1 gene showed a neoplastic leukemic clone possessing a full expansion of the CGG repeat, with associated aberrant methylation of the promoter CpG islands. However, analysis during morphologic remission showed that the promoter CpG island was apparently unmethylated in the regenerating normal hematopoietic cells. During subsequent relapses, the FMRI CGG repeat was unstable, with the appearance of multiple leukemic subclones possessing different repeat expansions. Our case suggested that deregulation of the FMR1 gene might have contributed to leukemogenesis in our case.