Essential Thrombocythemia (ET)

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Essential Thrombocythemia (ET)

Clinics and Pathology

Disease chronic myeloproliferative syndrome

Phenotype / cell stem origin The disease is a chronic myeloproliferative disorder originating from a mutated pluripotent stem cell capable of producing red blood cells, granulocytes and megakaryocytes. In some cases, B-lymphocyte involvement by the clonal proliferation was documented. T-lymphocytes are not involved by the malignant process and nonclonally derived granulocytes may coexist with clonal cells in patients with ET.

Epidemiology ET has an annual incidence of 1.5 to 2.4 patients /100,000. The disease incidence may show a peak around 30 years in females, with a second peak in the elderly with a 1:1 male-to-female ratio. The average age at diagnosis is 50-60 years.

Clinics The disease is diagnosed in the presence of a sustained increase of the platelet count (>600 X 10⁹/L) over at least 1 month without an obvious explanation.
In the majority of patients the disease remains asymptomatic for many years. The disease symptoms are usually related to arterial thrombosis and, less frequently, deep venous thrombosis, which are more frequent in the untreated patient. Death may occur following major ischemic events or leukemic transformation.

Cytology The peripheral blood smear shows thrombocytosis without obvious morphologic abnormalities of the white blood cells and erythrocytes. Megathrombocytes may be seen. The bone marrow is hypercellular with enlarged megakaryocytes, which may tend to aggregate in small clusters. At diagnosis a moderate increase of reticulin fibers may be observed, whereas the presence of marked fibrosis is a diagnostic exclusion criteria.

Treatment Treatment should be considered for patients at risk of thrombosis (age > 60 years, previous ischemic events, platelet > 1500 X 10⁹/L). Low-dose aspirin or other anti-platelet agents are used. Hydroxyurea is effective in reducing the platelet count and the incidence of thrombotic events. Interferon or anagrelide may be used in young patients.

Evolution Leukemic transformation may occur in 3-10% of the cases. Transformation into a stage indistinguishable form idiopathic myelofibrosis was documented in 5% of the cases.

Prognosis The large majority of the patients survive >10 years. No significant difference between life expectancy of ET patients and age-matched subjects was observed in a study.

Cytogenetics

Cytogenetics Morphological Less than 10% of the patients show a clonal chromosome defect at diagnosis. Recurrent abnormalities include total/partial trisomy 1q, trisomy 8 and trisomy 9, del(13q) and del(20q). Rearrangements of Chromosome 17, leading to 17p deletion can be frequently associated with Leukemic transformation.

Cytogenetics Molecular a) Fluorescence in situ hybridization (FISH) and molecular studies :
FISH may be more sensitive than conventional karyotyping for the detection of chromosome deletions
b) Janus Kinase JAK2 mutation :
A valine to phenylalanine substitution at position 617 (JAK2 V617F mutation) is present in 50-75% of the patients leading to constitutive kinase activity. Unlike polycythemia vera, mutated homozygous cells are not found in ET. In 1% of the patients a gain-of-function mutation of the thrombopoietin receptor (MPL) gene can be found, determining activation of the JAK-STAT pathway

Bibliography

Evidence for the involvement of B lymphoid cells in polycythemia vera and essential thrombocythemia.

Raskind WH, Jacobson R, Murphy S, Adamson JW, Fialkow PJ

The Journal of clinical investigation. 1985 ; 75 (4) : 1388-1390.

PMID 3921571

Cytogenetic analysis in essential thrombocythemia at diagnosis and at transformation. A 12-year study.

Sessarego M, Defferrari R, Dejana AM, Rebuttato AM, Fugazza G, Salvidio E, Ajmar F

Cancer genetics and cytogenetics. 1989 ; 43 (1) : 57-65.

PMID 2790773

Life expectancy of patients with chronic nonleukemic myeloproliferative disorders.

Rozman C, Giralt M, Feliu E, Rubio D, Cortˆ©s MT

Cancer. 1991 ; 67 (10) : 2658-2663.

PMID 2015567

Clonality analysis of hematopoiesis in essential thrombocythemia: advantages of studying T lymphocytes and platelets.

el-Kassar N, Hetet G, Briˆ®re J, Grandchamp B

Blood. 1997 ; 89 (1) : 128-134.

PMID 8978285

Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion.

Sterkers Y, Preudhomme C, LaˆØ JL, Demory JL, Caulier MT, Wattel E, Bordessoule D, Bauters F, Fenaux P

Blood. 1998 ; 91 (2) : 616-622.

PMID 9427717

Cytogenetic and molecular genetic aspects of essential thrombocythemia.

Steensma DP, Tefferi A

Acta haematologica. 2002 ; 108 (2) : 55-65.

PMID 12187022

Incidence of trisomy 8 and 9, deletion of D13S319 and D20S108 loci and BCR/ABL translocation in non-treated essential thrombocythemia patients: an analysis of bone marrow cells using interphase fluorescence in situ hybridization.

Zamora L, Espinet B, Florensa L, Besses C, Salido M, Solˆ© F

Haematologica. 2003 ; 88 (1) : 110-111.

PMID 12551834

Management of polycythemia vera and essential thrombocythemia.

Campbell PJ, Green AR

Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program. 2005 : 201-208.

PMID 16304381

Essential thrombocythemia.

Fruchtman SM, Hoffman R IN: Hematology Basic Principles and practice Hoffman R, Benz EJ, Shattil SJ, Furie B, Cohen HJ, Silbertsein LE, McGlave P Eds

Elsevier, Philadelphia, Pennsylvania,. 2005.

MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients.

Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M, Steensma DP, Elliott MA, Wolanskyj AP, Hogan WJ, McClure RF, Litzow MR, Gilliland DG, Tefferi A

Blood. 2006 ; 108 (10) : 3472-3476.

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Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia.

Scott LM, Scott MA, Campbell PJ, Green AR

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PMID 16772604

Contributor(s)

Written 08-1997 Jean-Loup Huret

Updated 02-1998 Jean-Loup Huret

Updated 08-2006 Antonio Cuneo, Francesco Cavazzini

Citation

This paper should be referenced as such :
Huret JL . Essential Thrombocythemia (ET). Atlas Genet Cytogenet Oncol Haematol. August 1997 .
URL : http://AtlasGeneticsOncology.org/Genes/ET.html

Huret JL . Essential Thrombocythemia (ET). Atlas Genet Cytogenet Oncol Haematol. February 1998 .
URL : http://AtlasGeneticsOncology.org/Genes/ET.html

Cuneo A, Cavazzini F . Essential Thrombocythemia (ET). Atlas Genet Cytogenet Oncol Haematol. August 2006 .
URL : http://AtlasGeneticsOncology.org/Genes/ET.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Dec 6 18:01:25 2008

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For comments and suggestions or contributions, please contact us

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Disease	chronic myeloproliferative syndrome
Phenotype / cell stem origin	The disease is a chronic myeloproliferative disorder originating from a mutated pluripotent stem cell capable of producing red blood cells, granulocytes and megakaryocytes. In some cases, B-lymphocyte involvement by the clonal proliferation was documented. T-lymphocytes are not involved by the malignant process and nonclonally derived granulocytes may coexist with clonal cells in patients with ET.
Epidemiology	ET has an annual incidence of 1.5 to 2.4 patients /100,000. The disease incidence may show a peak around 30 years in females, with a second peak in the elderly with a 1:1 male-to-female ratio. The average age at diagnosis is 50-60 years.
Clinics	The disease is diagnosed in the presence of a sustained increase of the platelet count (>600 X 10⁹/L) over at least 1 month without an obvious explanation. In the majority of patients the disease remains asymptomatic for many years. The disease symptoms are usually related to arterial thrombosis and, less frequently, deep venous thrombosis, which are more frequent in the untreated patient. Death may occur following major ischemic events or leukemic transformation.
Cytology	The peripheral blood smear shows thrombocytosis without obvious morphologic abnormalities of the white blood cells and erythrocytes. Megathrombocytes may be seen. The bone marrow is hypercellular with enlarged megakaryocytes, which may tend to aggregate in small clusters. At diagnosis a moderate increase of reticulin fibers may be observed, whereas the presence of marked fibrosis is a diagnostic exclusion criteria.
Treatment	Treatment should be considered for patients at risk of thrombosis (age > 60 years, previous ischemic events, platelet > 1500 X 10⁹/L). Low-dose aspirin or other anti-platelet agents are used. Hydroxyurea is effective in reducing the platelet count and the incidence of thrombotic events. Interferon or anagrelide may be used in young patients.
Evolution	Leukemic transformation may occur in 3-10% of the cases. Transformation into a stage indistinguishable form idiopathic myelofibrosis was documented in 5% of the cases.
Prognosis	The large majority of the patients survive >10 years. No significant difference between life expectancy of ET patients and age-matched subjects was observed in a study.

Written	08-1997	Jean-Loup Huret

Updated	02-1998	Jean-Loup Huret

Updated	08-2006	Antonio Cuneo, Francesco Cavazzini