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?

b. What is the first-line treatment for CML and what is the rationale for this pharmacotherapy?

c. What are the mechanisms of resistance to imatinib pharmacotherapy of CML?

d. What other cancers and diseases are effectively treated with imatinib?

e. What are the common and important side effects of therapy with imatinib,

Answer 1

A.Philadelphia chromosome (Ph): The chromosome abnormality that causes chronic myeloid leukemia (CML). Abbreviated as the Ph chromosome. The Ph chromosome is an abnormally short chromosome 22 that is one of the two chromosomes involved in a translocation (an exchange of material) with chromosome 9.
The swapping of DNA between the chromosomes leads to the formation of a new gene (an oncogene) called BCR-ABL. This gene then produces the BCR-ABL protein, which is the type of protein called a tyrosine kinase.

B. Dasatinib and nilotinib is given as drug. They are tyrosinase kinase inhibitors.

C. They inhibit tyrosinase kinase which further inhibits the oncogene produced BCR -ABL protein.

D. Leukamia, gastrointestinal stromal tumors etc are treated using imatinib.