CML lecture

Question 1

chromosome responsible for CML

Answer 1

philidelphia chromo

Question 2

3 phases of CML progression

Answer 2

1. chronic
2. accelerated
3. blast crisis

Question 3

CML therapy in 70s and effect

Answer 3

cytoreductive agents - lower WBC counts, no effect on survival

Question 4

CML therapy in 80s and effect

Answer 4

interferon - blast crisis deferred

- toxic

Question 5

CML therapy in 90s and effect

Answer 5

marrow transplant

• cures some
• kills many early

Question 6

important findings in 60s

Answer 6

philidelphia chormo - CML cells have genetic changes

Question 7

important findings in 73

Answer 7

philadelphia gene is a translocation problem

Question 8

important findings in 83

Answer 8

c-abl - oncogene on chromosome 9

clustered in small area (bcr)

Question 9

important findings in 85

Answer 9

translocation results in fusion mRNA that is part BCR, part ABL

Question 10

important findings in 90

Answer 10

BCR-ABL encodes a kinase with altered activity

Question 11

other important findings in 90

Answer 11

BCR-ABL expression is sufficient to cause leukemia

Question 12

what is BCR-ABL

Answer 12

kinase oncogene that transfer P to activate leukemia

Question 13

what does imatinib do?

Answer 13

competitive inhibitor of ATP binding in BCR-ABL

Question 14

how does CML become imatinib resistant?

Answer 14

kinase domain mutation - changes shape of receptor so imatinib can’t bind, but ATP can still bind

Question 15

what has happened now

Answer 15

more kinase inhibitors have been produced