MPN Flashcards
Ddx for MF
Primary vs secondary
Fibrotic mds
CMML
High risk mutation for MF
Asxl-1, EZH-2, IDH1/2 srsf2 sf3B1
Criteria for SM- one major and one minor or 3 minor
Maj- dense infiltrates if last cells on bm or extra jag dois organs
Minor
>25% mast cells in i filtrate are spindle shaped or have atypical morphology
Detection of kit on bm blood or EC organ
MC express CD 2 and or cd25 in addition to Normal mast cell markers
Sérum tryptase exceeds 20
Criteria for CEL
Oes > 1.5 and increased in bone marrow
No ph chromosome nor bcr abl fusion gene or other mpn(pcv, ET, MF) or mds
Mon
There is fip1l-pdgfra fusion gene or another re arrangement of pdgfra
No fgfr1 re arrangement
BMBC<20% and no inv 16 or t 16:16
Clonal cytogenetic or molecular marker or blasts are more than 2% in blood 5% in marrow
Clinical features of fip1l1- pdgfra HES
Males> females Elevated tryptase Elevated b12 Spleen Hyper cellular and fibrotic marrow Dysplastic mast cells Anaemia thrombocytopenia
PDGFRB re arrangements - dx you see
CEL
aCML or MPN
CMML
32 fusion partners w most common being hyub
ET - all 4 major or first 3 + minor
Plt > 450
BM- meg prolog- buperlobated nuclei
Not meeting who criteria for other myeloid neoplasms
Jak2, calR, or MPL
Minor- presence of clonal marker or absence of evidence for reactive
PF- MF
All 3 major plus one minor
Mega prolif and atypia w no fibrosis w inc cellularity, gran prolif, and déc erythropoiesis
Not meeting WHO for other neoplasm
Présence jak2, calR,. Or MPL or other clonal marker
Présence of one of je following on 2 occasions-
Anaemia
WCC> 11
Palpable splénomégalique
LdH inc
Criteria pcv
3 major or first 2 major and minor 1 erythrocytosis > 6 mths 2bone marrow demonstrating mpn features 3. Jak mutation 4. Low serum epo
Molecular dx pcv
95% ja2 v617 f on exon 14 within kinase domain
5% exon 12 mutation
Methods for jak2 exon 12
PCR high resolution melt
Because there are so many sites for this mutation
The products will melt at different t temps if there is a mutation
IHC for mast cell on marrow
CD 117(kit) Tryptase
Mast cell leukaemia-
> 20% mc on aspirate not trephine
Strong CD 30 in most neoplastic mc indicates aggressive dx(either agg MCL or mcl)
Flow neoplastic mast cells
CD 2 CD 25 bright cd 30
What is cal r mutation
Either 2-5 bp deletions or insertions in last exon
High jak 2 v617f allèle burden in PMF
Correlated with enhanced myelopoieis of bm
Leukocytosis
Inc spleen size
Circulating CD 34 positive cells and inversely correlates w plt count
Criteria for a CML
Wbc 13 duye to neuts w promineng dysplasia
Neutrophils precursers greater 10%
Ph negative and mo f cfiteria pcv, mf, et
No pdgfra, b fgr1 or pcm jak
Minimal basophilia
Low monocytes
Hypercelller marrow w gran prolif and dysplasia
<20% blasts
Setpb1
33%aCML
Assooc w higher wcc lower hb N plts and worse os anbd may be asoc w isochromoskme 17
Can be found in tandem w csfr3r
Mutualky exclusive of jak tet
5;12)(q33-q13;p12) translocation. What gene rearrangement is associated with this translocation?
Pdgfrb etv asoc w cmml usually with esinophilia
To what sens should you down to for jak 2
1%
Mutat iii n nhibitors u scfreen for in 5q nds beforehand
Tp53
High risk mds
Complex >3
Low risk
5q, srf3b1, 11q, 20p
Main molecular abnormality in all
BCR-ABL / t(9;22)(q34;q11)MLL-AF4 / t(4;11)(q21;q23)TEL-AML1 / t(12;21)(p13;q22)E2A-PBx 1/ t(1;19)(q23;p13)E2A-HLF / t(17;19)(q22,p13)MLL-v / t(11;v)(q23;v)c-MYC-IgH / t(8;14)(q24;q32)IL3-IgH / t(5;14)(q31;q32)
