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Journal of Medical Oncology & Therapeutics | Volume 4
March 18-19, 2019 | London, UK
Oncology & Cancer Therapy
International Conference on
The JAK2V617F mutated trilinearmyeloproliferativeneoplasms
(MPN) include a broad spectrum of clinical laboratory
and bone marrow features in essential thrombocythemia
(ET), prodromal polycythemia vera (PV) and erythrocythemic
PV, classical PV and advanced stages of masked PV and PV
complicated by splenomegaly and secondary myelofibrosis
(MF). Heterozygous JAK2V617F mutated ET is associatedwith low
JAK2alleleandMPNdiseaseburdenandnormallifeexpectance.
In combined heterozygous and homozygous or homozygous
JAK2V617F mutated trilinear MPN, the JAK2 mutation load
increases from less than 50% in prodromal and early stage PV
to above 50% up to 100%in classical PV, advanced PV and PV
withMF. Bonemarrowhistology features showvarious degrees
of diagnostic erythrocytic, megakaryocytic and granulocytic
(EMG) myeloproliferation in JAK2V617F mutated trilinear MPN
clearly differ from monolinear megakaryocytic (M) in MPL or
dual megakaryocytic granulocytic (MG) myeloproliferation
in calreticulin (CALR) mutated thrombocythemia without
features of PV. The morphology of clustered large
pleomorphic megakaryocytes with hyperlobulated nuclei
are similar in JAK2V67F thrombocythemia, prodromal PV
and classical PV patients. Monolinear megakaryocytic (M)
myeloproliferation of large to giant megakaryocytes with
hyperlobulated staghorn like nuclei is the hallmark of MPL515
mutated normocellular thrombocythemia. CALR mutated
thrombocythemia usually presents with high platelet count
around 1000x109/l and normocellular megakaryocytic (M)
proliferation of immature megakaryocytes with cloud-like
hyperchromatic nuclei or prefibrotic dual megakaryocytic
granulocytic (MG) myeloproliferation followed by various
degrees of bone marrow fibrosis. Natural history and life
expectancy of MPN patients are related to the response
to treatment and the degree of anemia, splenomegaly,
myelofibrosis and constitutional symptoms. The acquisition
of epigenetic mutations at increasing age on top of MPN
disease burden independently predict unfavorable outcome
in JAK2V617F, MPL515 and CALR mutated MPNs, which mutually
exclude each other. Current treatment options in MPN include
low dose aspirin in JAK2 and MPL mutated ET, phlebotomy on
top of aspirin in PV, pegylated interferon in intermediate stages
of PV and CALR and MPL mutated ET followed by hydroxyurea
and or ruxolitinib in the hypercellular stages of PV and MF.
Speaker Biography
Jan Jacques Michiels is a Lifestyle Physician and Medical Doctor, MD, educated
in Internal Medicine, Hematology, Bloodcoagulation and Vascular Medicine and
graduated as PhD at the Erasmus University Medical Center, Rotterdam. He frequently
served as Guest Editor and was the Founder and Editor in Chief of Seminars in Vascular
Medicine. He is the Founder of the Thrombocythemia Vera Study Group, the European
Working Group on Myeloproliferative Disorders and Myeloproliferative Neoplasms as
scientific working groups of the European Hematology Association. He is the founder
of the Goodheart Institute & Foundation in Nature Medicine & Health, Rotterdam, The
Netherlands.
e:
Jan Jacques Michiels
Goodheart Institute, The Netherlands
The PVSG/WHO versus the clinical, laboratory, molecular and pathological (2018
CLMP) defined myeloproliferative neoplasms caused by JAK2V617F JAK2 EXON12,
CALR, MPL and TPO driver mutations are distinct blood & coagulation disorders:
Prognostic and therapeutic implications towards 2020 and beyond