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alliedacademies
Archives of General Internal Medicine | Volume 2
&
April 04-05, 2018 | Miami, USA
International Conference on
Internal Medicine & Practice and Primary Care
International Meeting on
Breast Pathology & Cancer Diagnosis
The 2008 World Health Organization (WHO) criteria do not
define the prodromal and advanced or masked stages of the
myeloproliferativeneoplasms(MPN)essentialthrombocythemia
(ET) and polycythemia vera (PV). Bone marrow biopsy (BMB)
has a near to 100% sensitivity and specificity to distinguish
thrombocythemia in BCR/ABL positive CML and ET, and the
myelodysplastic syndromes in RARS-T and 5q-minus syndrome
from thrombocythemia in myeloproliferative disorders (MPD).
Bone marrow pathology combined with JAK2, MPL and JAK2
exon 12 mutation detection is a pathognomonic clue to each
of the MPNs. Each of the JAK2 trilinear MPN markers including
spontaneous endogenous erythroid colony (EEC) formation,
low serum erythropoietin (EPO) levels, and JAK2 mutations
are specific but not sensitive enough to distinguish ET and PV.
The combination of JAK2 mutation and increased erythrocytes
(>6x109/L), haematocrit (>0.51 males and >0.48 females) is
diagnostic for PV (specificity 100%, sensitivity 95%) obviates
the need of red cell mass measurement. About half of WHO-
defined ET and MF patients are JAK2 positive. According
to 2008 ECMP criteria, JAK2 mutated ET comprises three
distinct phenotypes of normocellular ET, ET with increased
bone marrow erythropoiesis and hyper cellular ET with
megakaryocytic granulocytic myeloproliferative without leuko-
erythroblastosis. Low vs. high JAK2 allele and MPN disease
burden in heterozygous ET vs. homozygous PV is of major
clinical and prognostic significance. JAK2 wild type MPL mutated
normocellular ET is the second distinct MPN. JAK2/MPL wild
type hypercellular ET with primary megakaryocytic granulocytic
myeloproliferative (PMGM) is the third distinct MPN. CALR
mutated ET and MF lack PV features in blood and bone marrow.
Pre-treatment bonemarrowhistology distinguishes JAKmutated
trilinear MPN from calreticulin (CALR) and MPL mutated MPN.
Increase of clustered large pleomorphic megakaryocytes with
hyper lobulated nuclei is similar in JAK ET and PV patients.
CALR mutated thrombocythemia shows characteristic
bone marrow features of primary dual megakaryocytic
granulocytic myeloproliferative (PMGM) without features of
PV. MPL mutated thrombocythemia is featured by large to giant
megakaryocytes with hyper lobulated stag horn like nuclei in a
normocellular bone marrow without features of PV. Increase of
JAK2, CALR and MPL MPN disease burden is related the degree
of splenomegaly, myelofibrosis and constitutional symptoms
during life-long follow-up. The presence of epigenetic mutations
at increasing age predict unfavorable outcome in JAK2, CALR and
MPL mutated MPNs. Low dose aspirin in ET and phlebotomy
on top of aspirin in PV is mandatory to prevent platelet-
mediated microvascular circulation disturbances. Pegylated
interferon is the first line myeloreductive treatment option in
prodromal and early stage JAK2 mutated PV and in CALR and
MPL mutated thrombocythemia. Low dose pegylated interferon
in symptomatic is the first myeloreductive treatment of choice
to postpone or eliminate the use of hydroxyurea as long as
possible.
e:
The 2001-2016 World Health Organization vs. European clinical, molecular and pathological and the
2008-2018 clinical, laboratories, molecular and pathological (CLMP): Euro-Asian classification of JAK2,
CALR and MPL mutated myeloproliferative neoplasms
Jan Jacques Michiels
Antwerp University Hospital, Netherlands