Lec 17 - Chronic Myeloid Leuk

Question 1

what is Gleevec

Answer 1

the first molecular targetted therapy to have significant reported success

Question 2

how is chronic diff to acute in terms of the cells they affect

Answer 2

mainly affect mature granulocytes (and some precursors, but mainly mature cells)

Question 3

how is it diff to acute when considering age of patient

Answer 3

can occur at any age

Question 4

what chromosome and mutation is characteristic of this

Answer 4

Philadelphia chromosome (the fused end product)
translocation from chrom 9 to 22
BCR-ABL1

Question 5

what 2 genes are fused in this translocation

Answer 5

ABL = protooncogene - on chrom 9
BCR = normal gene - on chrom 22

Question 6

what does the BCR-ABL gene encode for

Answer 6

protein that causes production of tyrosine kinase
= stimulates continuous production of abnormal blood cells

Question 7

effect of BCR-ABL gene

Answer 7

increased cell cycling
resistance to apoptosis

Question 8

how can you visualise the philadelphia chromosome

Answer 8

cytogenetics
and
by fluorescence in situ hybridisation
(FISH)

Question 9

presenting clinical features

Answer 9

• weight loss
• night sweats
• splenomegaly
• anaemia
• bleeding, bruising

Question 10

how are 50% of cases diagnosed

Answer 10

incidentally from routine blood counts

Question 11

common lab findings

Answer 11

• leukocytosis (lots of white cells in bloo dsample)
• increased basophils (very uncommon usually, so abnormal to see them)
• hypercellular bone marrow

Question 13

3 phases of CML

Answer 13

• chronic phase (CML-CP)
• accelerated phase (CML-AP)
• blast phase (CML-BP

Question 14

characteristics of chronic phase

Answer 14

can be assymptomatic for 5-6 years
responds well to chemo = can remain in chronic phase for longer

Question 15

characteristics of accelarated phase

Answer 15

• new cytogenetic abnormalities
• increased number of blasts
• symptoms appear

Question 16

characteristics of blast phase :/

Answer 16

develops into fatal acute leukemia
poor prognosis

Question 17

main treatment used

Answer 17

tyrosine kinase inhibitors
targets the specific effects of the altered chromosome

Question 18

what specfic treatments are licensed for use in newly diagnosed CML

Answer 18

imatinib
2nd gen:
- dasatinib
- nilotinib
(these are used if resistance to imatinib develops)

Question 19

mode of action of imatinib

Answer 19

• blocks binding of ATP to BCR-ABL
• which inhibits activity of the kinase
• and inibits proliferation of BCR- ABL cells

Question 20

why is imatinib being so specific not great

Answer 20

molecular resistance
so second generation drugs have been developed

Question 21

how is dasatinib diff to imatinib

Answer 21

basically works the same
but is a broader, multikinase inhibitor
so is used when resistance to imatinib is acquired