HAEM5:Essential thrombocythaemia: Difference between revisions

Approximately half of ET cases are asymptomatic at the time of diagnosis and are identified by an elevated platelet count by a routine peripheral blood count. The other half is diagnosed after a vascular occlusion or hemorrhage. Other cases present with symptoms including transient ischaemic attacks, and thrombosis of major arteries and veins.  Mild splenomegaly is present in approximately 50% of cases at diagnosis and hepatomegaly in 15-20 %<ref name=":0" />.

In a recent study, the most frequent ET patient symptoms were reported to be fatigue (90.3%), numbness (58.8%), insomnia (58%), sad mood (57.3%), vertigo (56,1%), concentration problem (55.8%), inactivity (53.7%), early satiety (53.2%), night sweats (51.3%), sexual problem (51.0%), headache (47.1% ), abdominal discomfort (45.3%), bone pain (45.2%), cough (41.4%), itching (40.6%), abdominal pain (38.2%), weight loss (23.4%) and fever (17%)<ref name=":1" />.

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==Sites of Involvement==

Flow cytometery results of ET samples typically includes normal number of phenotype myeloblasts with normal myeloid scatter by CD45/ SSC. There is no immunophenotypic evidence of myelodysplasia, (normal CD10/ CD13/ CD16/ CD11b myeloid maturation pattern). There is no evidence for monoclonal B cell lymphoproliferative disease and no unusual T cell phenotypes are identified<ref>{{Cite journal|date=[object Object]|title=Essential thrombocythemia|url=http://www.pathologyoutlines.com/topic/myeloproliferativeET.html}}</ref>.

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==Chromosomal Rearrangements (Gene Fusions)==

Very rarely, cases of ET acquire a BCR-ABL1 rearrangement. Consequently, in this situation, a morphological and hematological shift capable of chronic myeloid leukemia evolution may occur<ref>{{Cite journal|last=K|first=Hussein|last2=O|first2=Bock|last3=K|first3=Theophile|last4=A|first4=Seegers|last5=H|first5=Arps|last6=O|first6=Basten|last7=Kh|first7=Grips|last8=J|first8=Franz-Werner|last9=G|first9=Büsche|date=2008|title=Chronic myeloproliferative diseases with concurrent BCR-ABL junction and JAK2V617F mutation|url=https://pubmed.ncbi.nlm.nih.gov/17972958/|language=en|pmid=17972958}}</ref>

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* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

ET is characterized by overall favorable prognosis as compared to the other MPNs (PV and PMF) with an expected survival of 19.8 years; however, life-expectancy is still reduced compared to the control population. Incidence of blast transformation and fibrotic transformation is lower in ET as compared to PV<ref name=":1" />. Transformation of ET to a blast phase (AML or MDS) occurs in <5% of cases, and is likely related to previous cytotoxic therapy<ref name=":0" />.

The transformation of ET to AML and/or post-ET myelofibrosis (post-ET MF) are rare events. The risk of transformation to acute leukemia was reported to 2-3% at 10 years and 5% at 15 years after diagnosis. Risk factors included age and age over 60 years. Occurrence of post-ET myelofibrosis does occur rarely with a risk of 6% at 15 years. Anemia was identified as the only significant risk factor for development of post-ET myelofibrosis<ref>{{Cite journal|last=F|first=Passamonti|last2=E|first2=Rumi|last3=L|first3=Arcaini|last4=E|first4=Boveri|last5=C|first5=Elena|last6=D|first6=Pietra|last7=S|first7=Boggi|last8=C|first8=Astori|last9=P|first9=Bernasconi|date=2008|title=Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients|url=https://pubmed.ncbi.nlm.nih.gov/18790799/|language=en|pmid=18790799}}</ref>  

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==Individual Region Genomic Gain / Loss / LOH==

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Uniparental disomy (UPD) in Essential Thrombocythemia has not been reported. Conversely, UPD of chromosome 9p (typically causing homozygosity of JAK2 pathogenic variants) is a frequent clonal occurrence in polycythemia vera (PV) <ref>{{Cite journal|last=Kralovics|first=R|date=2002|title=Acquired uniparental disomy of chromosome 9p is a frequent stem cell defect in polycythemia vera|url=https://linkinghub.elsevier.com/retrieve/pii/S0301472X01007895|journal=Experimental Hematology|volume=30|issue=3|pages=229–236|doi=10.1016/S0301-472X(01)00789-5}}</ref>.

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==Characteristic Chromosomal Patterns==

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An abnormal karyotype is found in 5-10% of cases; however, there is no consistent abnormality. Reported, but non-specific, abnormalities in ET include gain of chromosome 8, abnormalities of 9q, and del(20q). Isolated instances of del(5q) have also been reported in ET<ref name=":0" />.

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==Gene Mutations (SNV / INDEL)==

Most cases of ET harbor a phenotypic driver mutation in JAK2 (50-60% of ET cases), CALR (in 30%), or MPL (in 3%), and about 13% of ET are triple negative for these mutations. None of these mutations are specific for ET; however, the presence of these mutations would rule out reactive or secondary thrombocytosis<ref name=":0" />.  

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==Epigenomic Alterations==

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'''JAK2'''

Essential Thrombocythemia (ET) with CALR pathogenic variants has been proposed to be a distinct entity with a less severe course of disease compared with JAK2 mutations. ET patients with CALR-pathogenic variants were more often found to exhibit lower leukocyte and hemoglobin values, higher platelet counts, and to be male compared with JAK2-mutated ET patients. Additionally, a lower incidence of thrombosis was seen in CALR-mutated ET vs. JAK2-mutated ET. This information has the potential to further stratify ET patients based on the prognosis and severity of the disease  <ref>{{Cite journal|last=Rotunno|first=Giada|last2=Mannarelli|first2=Carmela|last3=Guglielmelli|first3=Paola|last4=Pacilli|first4=Annalisa|last5=Pancrazzi|first5=Alessandro|last6=Pieri|first6=Lisa|last7=Fanelli|first7=Tiziana|last8=Bosi|first8=Alberto|last9=Vannucchi|first9=Alessandro M.|date=2014|title=Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia|url=https://ashpublications.org/blood/article/123/10/1552/32375/Impact-of-calreticulin-mutations-on-clinical-and|journal=Blood|language=en|volume=123|issue=10|pages=1552–1555|doi=10.1182/blood-2013-11-538983|issn=0006-4971}}</ref><ref>{{Cite journal|last=E|first=Rumi|last2=D|first2=Pietra|last3=V|first3=Ferretti|last4=T|first4=Klampfl|last5=As|first5=Harutyunyan|last6=Jd|first6=Milosevic|last7=Nc|first7=Them|last8=T|first8=Berg|last9=C|first9=Elena|date=2014|title=JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes|url=https://pubmed.ncbi.nlm.nih.gov/24366362/|language=en|doi=10.1182/blood-2013-11-539098|pmc=PMC3945864|pmid=24366362}}</ref>.  

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==Genetic Diagnostic Testing Methods==