Bim and Mcl 1 proteins are identified targets for phosphorylation and subsequent increased proteasomal degradation with respect to posttranscriptional aftereffects of CD40 stimulation on CLL cells. represent common data of 3 experiments. PI3K Akt/PKB signaling to activate GSK3, which phosporylates Mcl 1, thus marking it for proteasomal degradation. In the case of CLL cells, our data c-Met inhibitor indicate that upon CD40 stimulation PKB phosphorylation was undetectable, the PI3 kinase inhibitor LY294002 did not trigger apoptosis, and the rate of Mcl 1 protein turn-over was not changed. This means that the increase in Mcl 1 protein is possibly controlled at the level of interpretation by a non PKBdependent mechanism, because Mcl 1 transcription in CLL cells was also not afflicted by CD40. Up to now another point of regulation new data from other experimental methods indeed details at repression of Mcl 1 via eIF initiation facets. If this system is operational under our experimental conditions and whether it might be associated with another recently Retroperitoneal lymph node dissection described pathway implicating antigen receptor/PI3 K/PKB signaling in influencing Mcl 1 levels47 remains to be determined. In contrast to the specific situation in AML cells, in primary CLL cells the ERK pathway looks not accountable for improved Mcl 1 protein, as the ERK chemical PD 98 059 didn’t stop its increase, and did not affect drug susceptibility. If increased Mcl 1 plays an important role in vivo in success of CLL in lymph nodes seems an important issue with respect to therapeutic application of ABT 737. Our data and those of others31,41 show that variations in Mcl 1 and probably also A1/Bfl 1 levels will determine the effective dose of ABT 737 both as a single agent and in drug combinations. Of note, the combination of ABT 737 with roscovitine, which should fight HCV protease inhibitor Mcl 1,31, Bcl XL, and Bcl 2 was not effective in every patients. This suggests that either roscovitine is not able to lower Mcl 1 in this setting, or that perhaps in these samples A1/Bfl 1 is really a dominant factor. Our observations on increased Bim EL turnover are in accord with an established process of ERK mediated phosphorylation and proteasomal degradation. To your knowledge, this will be the first example of this pathway operating in primary tumor cells upon CD40 stimulation, and in CLL LN samples. Within our experience, neither imatinib or dasatinib are efficient inducers of apoptosis as single agents, in contrast to their effects on K562 cells, which rely for survival on the BCR Abl fusion oncogene. In a recent study, considerable difference in apoptosis vulnerability in neglected and dasatinib treated peripheral blood samples was found using 5 M dasatinib, and the response was linked with ZAP70 status and IgVH mutation. This and other studies performed so far agree that in CLL cells from peripheral blood,