10 / 16
Page 39
Volume 2
July 24-25, 2019 | Rome, Italy
World Hematology 2019 & Nursing Care 2019
July 24-25, 2019
Journal of Blood Disorders and Treatment
47
th
WORLD CONGRESS ON NURSING CARE
11
th
WORLD HEMATOLOGY AND ONCOLOGY CONGRESS
&
J Blood Disord Treat, Volume 2
2020 Clinical, Laboratory, Molecular and Pathological (CLMP) criteria for diagnosis
and new treatment options of JAK2
V617F
, JAK2 exon 12, CALR and MPL
515
mutated
Myeloproliferative Neoplasms: From Dameshek to Vainchenker, Kralovics, Tefferi and
Michiels 1940-2020
Jan Jacques Michiels
1,4
, Vasily Shuvaev
2
, Adrian Trifan
3
, Zwi Berneman
4
, Wilfried Schroyens
4
, Hendrik De Raeve
5
,
King Lam
6
, Achille Pich
7
, Vincent Potters
8
, Francisca Valster
8
, Yonggoo Kim
9,10
, Myungshin Kim
9,10
1
International Hematology and Bloodcoagulation Research Center, Goodheart Institute and Foundation in Nature Medicine, and
International Collaboration and Research on Myeloproliferative Neoplasms: ICAR.MPN, Rotterdam, The Netherlands
2
Hematology Clinic in Russian Research Institute of Hematology and Transfusiology, Saint-Petersburg, Russia
3
Department of Medical Genetics, “Luliu Hatieganu”, University of Medicine and Pharmacy, and Department of Genetics, “Ion Chiricuta”
Cancer Institute, Cluj-Napoca, Romania
4
Department of Hematology, University Hospital Antwerp, Edegem, Belgium
5
Departments of Pathology, OLV Hospital Aalst and University Hospital Brussels, Belgium
6
Department of Pathology, Erasmus University Medical Center EUMC, Rotterdam, The Netherlands
7
Department of Pathology and Hematology, Bravis Hospital, Bergen op Zoom, The Netherlands
8
Department of Molecular Biotechnology and Health Sciences, Section of Pathology, University of Turin
9
Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea
10
Catholic Genetic Laboratory Center, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea
T
he JAK2
V617F
mutated trilinear myeloproliferative neoplasms (MPN) is featured by clinical phenotypes ranging from
essential thrombocythemia (ET), prodromal polycythemia vera (PV), erythrocythemic PV, classical PV, masked PV and
PV complicated by splenomegaly and myelofibrosis (MF). The JAK2
V617F
mutation load increases from below 30% in ET to
above 50% in PV and further increases to 80% to 100% due to mitotic recombination of chromosome 9p from heterozygous
into heterozygous homozygous and homozygous (9p loss of heterogeneity: 9pLOH) in PV and MF. Bone marrow histology of
clustered increase of large pleomorphic megakaryocytes (M) with hyperlobulated nuclei are similar in JAK2
V617F
normocellular
ET, prodromal PV and classical PV. Bone marrow cellularity sequentially increases in JAK2
V617F
mutated ET and PV due to
erythromegakaryoytic (EM) and trilinear erythron-megakaryo-granulocytic (EMG) proliferation.
Two main variants of megakaryocytic leukemia (Dameshek 1951) or ET with platelet counts around 1000x109/L and no
features of PV include MPL
515
and CALR mutated thrombocythemia. Bone marrow histology in MPL
515
thrombocythemia is
featured by megakaryocytic myeloproliferation (M) of large to giant megakaryocytes with hyperlobulated staghorn like nuclei
in a normocellular bone marrow. Bone marrow histology of CALR thrombocythemia is characterized by megakaryocytic (M)
myeloproliferation of large to giant immature megakaryocytes in a normocellular bone marrow followed by primary dual
megakaryocytic granulocytic myeloproliferation (PMGM). Natural history and life expectancy of JAK2
V617F
, MPL
515
and CALR
mutatedMPNpatients are related to the response to treatment, the degree of anemia, splenomegaly, myelofibrosis and constitutional
symptoms. Epigenetic mutations at increasing age predict unfavorable outcome in adanced stages of JAK2
V617F
, CALR and MPL
mutated MPN. Low dose aspirin in JAK2
V617F
, MPL
515
and TPO mutated ET and phlebotomy on top of aspirin in prodromal and
classical PV will prevent platelet-mediated microvascular and major thrombotic events (Sticky Platelet Syndrome). Pegaylated
interferon (IFN) in JAK2
V617F
ET and PV and IFN or anagrelide in CALR and MPL
515
mutated thrombocythemias without
features of PV are first line treatment options for the control of platelet count to prevent thrombohemorrhagic complications and
for the control of MPN disease burden and spleen size to improve survival and quality of life. Ruxolitinib deserves a better place
in the treatment of hypercellular PV to reduce MPN disease burden in symptomatic hypercellular PV before significant marrow
fibrosis and splenomegaly do occur.