Genetics in Haematoncology II Flashcards
(33 cards)
Symtoms of MPN
Often asymptomatic with incidental findings
But increased risk of thrombosis, often in unusual sites, risk of Acute leukaemia or fibrosis
Findings in PCV
Raised Hb and HCT, much hihger RBC:Plasma ration, normal platelets
Findings in ET
Raised platelets, normal HB and Hcy
Describe frequency of JAK2 mutations in MPN
PCV 95%
ET 50-70%
PMF 40-50%
What is JAK2
Non-receptor TK, responds to ctokine signalling e.g. TPO, EPO, GCSF
What mutations often occur in JAK2
Exon 14 mutation at V617F causes constitutive phosphorylation and activation
Mutations in exon 12 can also ocur
What mutation other than JAK2 commonly occurs in MPN
MPL (the TPO Receptor)
8% PMF
4% ET mutations
What mutations other than JAKs or MPL occur in MPN
CALReticulin mutations
CALR normally functions in the ER as part of quality control and in the cytoplasm as a regulator of proliferation, apoptopsos, phagocytsis and immune function
Where do mutations in CALR usually occur
In exon 9 –> +1 base pair frameshift mutation which replaces the C terminus with a novel protein sequency
Converts it from acidid to basic structure
Which MPNs does CALR occur in
ET and PMF
DOES NOT OCCUR IN PCV
HOW do patients with CALR mutations differ from those with JAK2 mutations
These patients have higher platelet coutns
Lower HB
and lower risk of thrombosis
Treatment of MPN
Venesection
Cytoreduction: Chemo, IFN, P32 (if old)
JAK2 Inhibitors
What MPN has the worst prognosis
PMF median 3-7 years and up to 30% AML Risk
What are the symptoms of NHL
enlarged lymph nodes Bone marrow suppresion B Symtpoms Extra nordal manifestations Spelno/hepatomegaly
What type of NHL is more curable
High grade
Why are B cells more common
AS normal B cell function relies on rapid proliferation and genetic recombination of the immunoglobulin gene
What is the translcoation in follicular lymphoma
t(14:18) –> places the bcl-2 oncogene in the presence of the IgH promter causes enhacnes anti-apoptotis effects
What are the 3 types of Burkitts
1) Endemic
2) sporadic
3) immune deficiency associatsedx
What is the charactreristc histological appearance of Burkitts
Starry sky due ot plentiful aooptosis and dividing rapidly
What mAB can be given to treat Burkitts
Rituximab to CD20 expressing B cells
Does BUrkitts have a good prognosis
Yes >80% cure rate
Targets in B NHL
B Cell receptor pathway BCL-2 inhibitors Epigenetic therapies Monoclonal AB Agents targgeting the programemd cell death axis Chimeric antigen receptor T cells
How can we inhibit the PI3K pathway in BCR
Idelalisib
How does PI3K work
Heterodimer comprosing of the regulatory and catalytic subunits
the delta and gamma from are expressed primarily in haematolymphoid organs which can allow for the targeting of treatment
