Generation of the Jak3 knockin model and hematologic disorders. (A) Proportion of JAK3 activating mutations in different types of human hematologic malignancies. The frequency of the JAK3^A572/573V compared with mutations affecting other residues is shown (data obtained from http://cancer.sanger.ac.uk/cosmic and previously reported studies.^{9,11,21,22,35,36}  (B) Representative western blots assessing the activity of mutant Jak3 and downstream pathways in thymocytes from 6- to 8-week-old Jak3^WT/WT, Jak3^KI/WT and Jak3^KI/KI mice. Representative values of band intensity relative to Jak3^WT/WT are indicated. (C) Absolute cell number in the bone marrow (BM), spleen (SP), thymus (Thy), and lymph node (LN) of Jak3^WT/WT (WT/WT), Jak3^KI/WT (KI/WT), and Jak3^KI/KI (KI/KI) mice (5 to 13 mice per group, 6-14 months old). Data represented as the mean ± standard error of the mean (SEM); P values are indicated (Student t test). (D) Paraffin-embedded spleen sections from 10-month-old mice were stained with hematoxylin and eosin (H&E) as well as with anti-CD3, anti-factor VIII (von Willebrand factor [vWF]), and anti-myeloperoxidase (anti-MPO) antibodies (original magnification ×100). (E) Representative fluorescence-activated cell sorting (FACS) plots assessing the proportion of CD3⁺ cells in the spleen of 10-month-old wild-type (WT) and KI/KI mice. (F) Anti-CD3 immunostaining showing of the skin of 10-month-old WT and KI/KI mice (original magnification ×100). AML, acute myeloid leukemia; B-ALL, B-cell acute lymphoblastic leukemia; CTCL, cutaneous T-cell lymphoma; DS-AMKL, Down syndrome–associated acute megakaryoblastic leukemia; FSC, forward scatter; JMML, juvenile myelomonocytic leukemia; MDS, myelodysplastic syndrome; NKCL, natural killer T-cell lymphoma nasal-type; T-ALL, T-cell acute lymphoblastic leukemia; T-PLL, T-cell prolymphocytic leukemia.