Question

A 37-year-old man is diagnosed with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).

a. What is the molecular mechanism that makes this kind of cancer?(1/2 page)

b. What is the first-line treatment for CML and what is the rationale for this pharmacotherapy?(1/4 page)

c. What are the mechanisms of resistance to imatinib pharmacotherapy of CML?(1/4 page)

d. What other cancers and diseases are effectively treated with imatinib?(1/4 page)

e. What are the common and important side effects of therapy with imatinib(1/4 page)

Answer 1

1- There occurs translocation from chromocome number 9 to number 12. This leads to BCR-ABL fusion.

BCR- ABL fusion leads to a constitutive tyrosine kinase which would carry out the proliferation unregulated.

2- First line treatment of CML is Imatinib . The rational for using this is that it precludes the binding site of ATP on the ABL protein. It interacts with Pnunit to prevent binding to ATP. No ATP , No tyrosine kinase activity due to phosphorylation of tyrosine by ATP would be seen.

3- Mutations in the kinase domains of BCR ABL becoming resistant to drug binding or expression of excessive quantities of BCR ABL gene are the major mechanism of developemenr of resistance to the drug.

4- Used in following cancers :

1- Leukemia

2- Gastrointestinal stromal tumors ( GIST)

3- Dermatofibrosarcoma

5th ques :

1- Low blood counts

2- skin rash

3- Edema

4- muscke cramps and bone pain

5- Hemorrhage

6- fever