Question

For background: Q6= tyrosine kinase inhibitors & Q8= MHC molecules

I need help with Q7 & Q9. I think Q7 is C but not sure. For Q9 I think it is phorbol myristate acetate since in my notes it says "Treatment of PMA and ionomycin on T cells can induce the effects of TCR stimulation" does this reasoning make sense?

Although the (Q-6) approaches of CML treatment have dramatically changed the treatment of CML by inducing long term overall survival rates higher than 90%, approximately one quarter of patients develop the resistance to the (Q-6) treatment at some point during therapy. Regarding the molecular mechanism that causes the resistance to Q-6 mediation, it has been shown that the generation of point mutations in the BCR-ABL kinase domain are the most frequent mechanisms of acquired resistance development. Therefore, it is necessary to develop a new drug for the treatment of refractory CML. Q-7: Which of the following would be most efficient, scientifically reasonable approach for a new drug development for refractory CML. A. Finding a new monoclonal antibody that inhibit BCR-ABL, B. Finding new phosphatase inhibitors targeting BCR-ABL C. Finding new tyrosine kinase inhibitors targeting BCR-ABL D. Find a new drug that can inhibit IKK enzyme to inhibit the BCR-ABL signaling pathway E. Finding an allosteric inhibitor designed to inhibit BCR-ABL by binding to a distinct and separate region of the enzyme domain. Q-8 and 9: The following figure is about T cell images exhibiting the distribution of the specific protein (Q- Figure for Q-8 and 9 8: - To visualize the distribution of (Q-8), pure T cells were cultivated in a cell- culture petri dish and then untreated or treated with (Q-9: . The cells were left untreated (A), or treated with (Q-9) and incubated in an optimal condition for 10 min (B). 30 min (C), 1 hour (D). 2 hours (E), 4 hours (F). 6 hours (G), or 24 hours (H). The cells were then stained with the antibody recognizing the protein (Q-8). As a result, these cell images (Figure for Q-8 and 9) show that (Q-8) was distributed throughout the cell when the cells were treated/stimulated with (Q-9).

Answer 1

Q7.

Answer C - Finding new tyrosine kinase inhibitors targeting BCR-ABL.

Small molecule drugs interrupt an active BCR-ABL, the factor causing CML, by interfering with ATP-dependent ABL tyrosine kinase.The BCR-ABL protein increases the growth of CML cells. This tyrosine kinase activity was targeted for CML treatment.Tyrosine kinase inhibitors (TKIs) has resulted in an overall survival rate greater than 90%.

Q9.

Answer E - phorbol myristate acetate

"Treatment of PMA and ionomycin on T cells can induce the effects of TCR stimulation" does this reasoning make sense? - Yes the reasoning provided is correct.

Ionomycin has the ability to transfer calcium through the membrane.Similarly PMA has the ability to activate Protien kinase which is an enzyme that helps in signal transmission.By this overall reaction synergy, T cell proliferation and subgroup CD4 and CD8 can be activated.TCR is a T cell receptor.TCR stimulation means that protien kinase enzyme helps the receptors to recognize the antigens.