Kinase-functional BTK is necessary for the development and expansion of TCL1 leukemia. (A) TCL1 protein expression is retained after the cross with the XID mouse. Splenic lymphocytes from a pool of 3 1-month-old female XID/TCL1 mice and 1-month-old female B6/TCL1 mice were purified and B cell selected using the EasySep Mouse B Cell Enrichment Kit (Stem Cell Technologies) and then lysed; 50 μg of protein from each mouse was used for western blot analysis of TCL1 protein expression. TCL1 is present in both the B6/TCL1 and the XID/TCL1 mice. (B) WT/TCL1 mice have a higher percentage of leukemic lymphocytes in the peripheral blood compared with XID/TCL1 mice. Peripheral blood flow cytometry for CD5 and CD19 was performed on 59 WT/TCL1 and 61 XID/TCL1 mice. XID/TCL1 mice had a lower percentage of leukemic CD5/CD19 coexpressing cells than did WT/TCL1 mice. (C) OS is improved for XID/TCL1 mice compared with WT/TCL1 mice. All male XID/TCL1 and WT/TCL1 mice born within a 1-year time period, which included 65 XID/TCL1 and 78 WT/TCL1 mice, were followed for survival. OS is significantly prolonged in the XID/TCL1 cohort (P < .0001).