Among them, mut-Stat3 strain mimics human hyper-IgE syndrome and STAT3 G421R strain displays T-cell dysregulation aiming to mimic primary immune deficiencies.14,15 We have recently developed a Stat5b mutant mouse line, in which we introduced a SNP changing tyrosine to phenylalanine in position 665 (Y665F).16 This mutation has been detected in multiple leukemia patients and was hypothesized to be pathogenic due to STAT5B hyperactivation.17,18 The mice, while displaying number of hematopoietic abnormalities, did not directly develop malignancies. This evidence concerns the gene STAT5B and Immunodeficiency.