Lec 17 - Chronic Myeloid Leuk Flashcards
what is Gleevec
the first molecular targetted therapy to have significant reported success
how is chronic diff to acute in terms of the cells they affect
mainly affect mature granulocytes (and some precursors, but mainly mature cells)
how is it diff to acute when considering age of patient
can occur at any age
what chromosome and mutation is characteristic of this
Philadelphia chromosome (the fused end product)
translocation from chrom 9 to 22
BCR-ABL1
what 2 genes are fused in this translocation
ABL = protooncogene - on chrom 9
BCR = normal gene - on chrom 22
what does the BCR-ABL gene encode for
protein that causes production of tyrosine kinase
= stimulates continuous production of abnormal blood cells
effect of BCR-ABL gene
increased cell cycling
resistance to apoptosis
how can you visualise the philadelphia chromosome
cytogenetics
and
by fluorescence in situ hybridisation
(FISH)
presenting clinical features
- weight loss
- night sweats
- splenomegaly
- anaemia
- bleeding, bruising
how are 50% of cases diagnosed
incidentally from routine blood counts
common lab findings
- leukocytosis (lots of white cells in bloo dsample)
- increased basophils (very uncommon usually, so abnormal to see them)
- hypercellular bone marrow
3 phases of CML
- chronic phase (CML-CP)
- accelerated phase (CML-AP)
- blast phase (CML-BP
characteristics of chronic phase
can be assymptomatic for 5-6 years
responds well to chemo = can remain in chronic phase for longer
characteristics of accelarated phase
- new cytogenetic abnormalities
- increased number of blasts
- symptoms appear
