Leukemia predisposition - Familial Leukemia

Background Background There is increasing evidence for an inherited predisposition to pediatric acute lymphoblastic leukemia (ALL). We and others have previously reported rare and highly penetrant variants in hematopoietic transcription factors (PAX5 and ETV6) and tumor suppressor genes (TP53) in both sporadic and familial ALL. IKZF1 encodes the founding member of the Ikaros family of zinc finger transcription factors, and is a critical regulator of lymphoid development. IKZF1 is frequently targeted by somatic deletions and mutations in high-risk BALL , particularly Ph+ and Ph-like ALL, and is associated with poor outcome. IKZF1 alterations have previously been shown to result in the acquisition of stem cell-like features, overexpression of adhesion molecules causing aberrant cell-cell and cell-stroma interaction, and decreased sensitivity to tyrosine kinase inhibitors. Genome-wide association studies have also identified an association between common polymorphisms at the IKZF1 locus and risk of developing ALL, however the 1*