HNRPK translation-regulatory activity is essential for BCR/ABL oncogenic potential. (Ai) Confocal microscopy on anti-HNRPK-stained 32D-BCR/ABL cells untreated and treated with the MAPK inhibitor PD098059 or with imatinib. (Aii) Effect of imatinib on the BCR/ABL-induced phosphorylation of MAPK ERK1/2. (Bi) Confocal microscopy on anti-HA-stained 32D-BCR/ABL cells ectopically expressing HA-tagged wild-type, dominant-active S284/353D, and dominant-negative S284/353A mutant HNRPK proteins. (Bii) Levels of ectopic wild-type and mutant HNRPK proteins. (C) Effect of wild-type, S284/353D, and S284/353A mutant HNRPK on growth factor-independent proliferation (i) and cytokine-dependent and independent clonogenic efficiency (ii) of 32D-BCR/ABL cells. Bars represent the mean ± SE of values from 3 different experiments. (Di) Effect of wild-type and HNRPK mutants on the tumorigenic potential of 32D-BCR/ABL cells. Cells (10⁶) were injected subcutaneously into SCID mice; tumor appearance and growth were monitored daily and mice were killed 15 days after injection. Bars represent the mean ± SE from the weight of 5 tumors for each group. (Dii) Effect of wild-type and S284/353A-HNRPK on the leukemogenic process induced in SCID mice by intravenous injection of BCR/ABL-expressing cells. Kaplan-Meier plot shows survival of mice injected with 32D-BCR/ABL cells expressing wild-type or S284/353A-HNRPK. The log-rank test evaluated the differences among survival distributions (P < .001). Inset shows spleens of 3 mice of each group killed 4 weeks after cell injection.