Eosinophilia Associated Neoplasms Flashcards
What doe PDGFR A/B mean?
Platelet derived growth factor A and B.
What are the categories of myeloid/lymphoid neoplasms with eosinophilia?
They are categorised into those with:
PDGFRA, PDGFRB and FGFR1 rearrangements,
(PCM1-JAK2 rearrangements are a provisional entry).
What is the most common rearrangement seen in myeloid/lymphoid neoplasms with PDGFRA?
What causes the pathogenicity of it? How do we detect it?
A deletion of CHIC2 - it isn’t visible cytogenetically, it is cryptic.
This lies between PDGFRA and FIP1L1 and it’s deletion fuses these 2 proto-oncogenes.
We have a FISH probe that can detect this cryptic deletion.
What else can cause myeloid/lymphoid neoplasms with PDGFRA rearrangement?
Translocations which involve 4q12 and fuse PDGFRA with another gene.
What is the most common cause of myeloid/lymphoid neoplasms with PDGFRB?
A t(5;12) translocation that rearranges ETV6 with PDGFRB.
Where is PDGFRB located?
5q31~33
What are the other causes of myeloid/lymphoid neoplasms with PDGFRB?
There are other rearrangements involving PDGFRB but all are cytogenetically visible.
What can neoplasms with PDGFRA or PDGFRB be treated with? What is the prognosis?
What about when treatment resistant mutations are present?
They respond really well to imatinib.
Prognosis is therefore good.
Resistance mutations are rare but tend to respond to alternatives such as dasatinib.
If we get an AML with eosinophilia and all tests are normal (AML FISH and karyotype) what additional testing should we consider?
FISH for PDGFRA-FIP1L1 - cryptic rearrangement so important to eliminate.
Other relevant rearrangements would be visible and delete by karyotype.
Where is FGFR1?
8p11
What is the most common rearrangement associated with FGFR1?
t(8;13)
What is the prognosis associated with FGFR1? Does this disease respond to imatinib?
Associated with a poor prognosis and aggressive disease.
Does not respond to imatinib.
What are the myeloid/lymphoid neoplasms with PDGFRA/B and FGFR1 driven diseases at risk of transforming into?
They can transform into either myeloid or lymphoid leukaemia dependant on additional driving mutations.
