Lec 17 - Chronic Myeloid Leuk Flashcards

1
Q

what is Gleevec

A

the first molecular targetted therapy to have significant reported success

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2
Q

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

A

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

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3
Q

how is it diff to acute when considering age of patient

A

can occur at any age

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4
Q

what chromosome and mutation is characteristic of this

A

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

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5
Q

what 2 genes are fused in this translocation

A

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

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6
Q

what does the BCR-ABL gene encode for

A

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

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7
Q

effect of BCR-ABL gene

A

increased cell cycling
resistance to apoptosis

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8
Q

how can you visualise the philadelphia chromosome

A

cytogenetics
and
by fluorescence in situ hybridisation
(FISH)

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9
Q

presenting clinical features

A
  • weight loss
  • night sweats
  • splenomegaly
  • anaemia
  • bleeding, bruising
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10
Q

how are 50% of cases diagnosed

A

incidentally from routine blood counts

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11
Q

common lab findings

A
  • leukocytosis (lots of white cells in bloo dsample)
  • increased basophils (very uncommon usually, so abnormal to see them)
  • hypercellular bone marrow
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12
Q
A
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13
Q

3 phases of CML

A
  • chronic phase (CML-CP)
  • accelerated phase (CML-AP)
  • blast phase (CML-BP
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14
Q

characteristics of chronic phase

A

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

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15
Q

characteristics of accelarated phase

A
  • new cytogenetic abnormalities
  • increased number of blasts
  • symptoms appear
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16
Q

characteristics of blast phase :/

A

develops into fatal acute leukemia
poor prognosis

17
Q

main treatment used

A

tyrosine kinase inhibitors
targets the specific effects of the altered chromosome

18
Q

what specfic treatments are licensed for use in newly diagnosed CML

A

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

19
Q

mode of action of imatinib

A
  • blocks binding of ATP to BCR-ABL
  • which inhibits activity of the kinase
  • and inibits proliferation of BCR- ABL cells
20
Q

why is imatinib being so specific not great

A

molecular resistance
so second generation drugs have been developed

21
Q

how is dasatinib diff to imatinib

A

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