Figure 4.

CDK6 Regulates NPM-ALK-Induced Disease Progression

(A) Cdk6^+/+, Cdk6^+/−, and Cdk6^−/− mice crossed with NPM-ALK transgenic (tg) mice developed a T cell lymphoma after several weeks (n ≥ 8; mean survival 120 [Cdk6^+/+], 143.5 [Cdk6^+/−], and 212 [Cdk6^−/−] days; ^∗∗p = 0.001).

(B) [³H]thymidine incorporation of NPM-ALK-transformed Cdk6^+/+ and Cdk6^−/− cells (n ≥ 3; ^∗p = 0.009).

(C) Immunoblot for CDK6 and p16^INK4a of NPM-ALK-transformed Cdk6^+/+ and Cdk6^−/− cells.

(D) Methylation-specific PCR of a part of the p16^INK4a promoter CpG island in NPM-ALK-transformed murine cells. The visible PCR product indicates the presence of methylated alleles. wt BM, bone marrow of a healthy mouse; pos. contr., control for methylated samples; neg. contr., control for unmethylated samples.

(E) Immunoblot for CDK6 of untransformed human T cells (three individually derived samples), human T-lymphoid leukemic cell lines (Sudhl1, CCRF, PEER), untransformed murine T cells (two individually derived samples), murine Cdk6^+/+ NPM-ALK-transformed cells, untransformed murine B cells, untransformed human B cells, and human B-lymphoid leukemic cell lines (SUP-B15).

(F) Immunoblot for CDK6 of untransformed human B cells (three individually derived samples), human B-lymphoid leukemic cell lines (SUP-B15, RL-7, JVM2), untransformed murine B cells (two individually derived samples), murine Cdk6^+/+ p185^BCR-ABL-transformed cells (three individually derived cell lines), and murine Cdk6^+/++Cdk6 p185^BCR-ABL-transformed cells (three individually derived cell lines).

Error bars indicate the mean ± SEM. See also Figure S4.