HAEM5:Essential thrombocythaemia: Difference between revisions
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{{DISPLAYTITLE:Essential thrombocythaemia}} | {{DISPLAYTITLE:Essential thrombocythaemia}} | ||
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours ( | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]] | ||
{{Under Construction}} | {{Under Construction}} | ||
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}}</blockquote> | }}</blockquote> | ||
<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples) | <span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span> | ||
==Primary Author(s)*== | ==Primary Author(s)*== | ||
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==Clinical Features== | ==Clinical Features== | ||
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table | Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span> | ||
{| class="wikitable" | {| class="wikitable" | ||
|'''Signs and Symptoms''' | |'''Signs and Symptoms''' | ||
| | |EXAMPLE Asymptomatic (incidental finding on complete blood counts) | ||
EXAMPLE B-symptoms (weight loss, fever, night sweats) | |||
EXAMPLE Fatigue | |||
EXAMPLE Lymphadenopathy (uncommon) | |||
|- | |- | ||
|'''Laboratory Findings''' | |'''Laboratory Findings''' | ||
| | |EXAMPLE Cytopenias | ||
EXAMPLE Lymphocytosis (low level) | |||
|} | |} | ||
<blockquote class='blockedit'>{{Box-round|title= | <blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}} | ||
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" />. | 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" />. | ||
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==Immunophenotype== | ==Immunophenotype== | ||
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table | Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span> | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
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!Finding!!Marker | !Finding!!Marker | ||
|- | |- | ||
|Positive (universal)|| | |Positive (universal)||EXAMPLE CD1 | ||
|- | |- | ||
|Positive (subset)|| | |Positive (subset)||EXAMPLE CD2 | ||
|- | |- | ||
|Negative (universal)|| | |Negative (universal)||EXAMPLE CD3 | ||
|- | |- | ||
|Negative (subset)|| | |Negative (subset)||EXAMPLE CD4 | ||
|} | |} | ||
<blockquote class='blockedit'>{{Box-round|title= | <blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}} | ||
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>. | 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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!Notes | !Notes | ||
|- | |- | ||
| | |EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC) | ||
EXAMPLE 30% (add reference) | |||
|Yes | |Yes | ||
|No | |No | ||
|Yes | |Yes | ||
| | |EXAMPLE | ||
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). | The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). | ||
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<blockquote class='blockedit'>{{Box-round|title= | <blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}} | ||
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> | 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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<blockquote class='blockedit'>{{Box-round|title= | <blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in: | ||
* Chromosomal Rearrangements (Gene Fusions) | * Chromosomal Rearrangements (Gene Fusions) | ||
* Individual Region Genomic Gain/Loss/LOH | * Individual Region Genomic Gain/Loss/LOH | ||
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==Individual Region Genomic Gain / Loss / LOH== | ==Individual Region Genomic Gain / Loss / LOH== | ||
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span> | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
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!Notes | !Notes | ||
|- | |- | ||
| | |EXAMPLE | ||
7 | 7 | ||
| | |EXAMPLE Loss | ||
| | |EXAMPLE | ||
chr7:1- 159,335,973 [hg38] | chr7:1- 159,335,973 [hg38] | ||
| | |EXAMPLE | ||
chr7 | chr7 | ||
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|Yes | |Yes | ||
|No | |No | ||
| | |EXAMPLE | ||
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). | Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). | ||
|- | |- | ||
| | |EXAMPLE | ||
8 | 8 | ||
| | |EXAMPLE Gain | ||
| | |EXAMPLE | ||
chr8:1-145,138,636 [hg38] | chr8:1-145,138,636 [hg38] | ||
| | |EXAMPLE | ||
chr8 | chr8 | ||
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|No | |No | ||
|No | |No | ||
| | |EXAMPLE | ||
Common recurrent secondary finding for t(8;21) (add reference). | Common recurrent secondary finding for t(8;21) (add reference). | ||
|} | |} | ||
<blockquote class='blockedit'>{{Box-round|title= | <blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}} | ||
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>. | 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== | ==Characteristic Chromosomal Patterns== | ||
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis | Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span> | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
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!Notes | !Notes | ||
|- | |- | ||
| | |EXAMPLE | ||
Co-deletion of 1p and 18q | Co-deletion of 1p and 18q | ||
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|No | |No | ||
|No | |No | ||
| | |EXAMPLE: | ||
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | ||
|} | |} | ||
<blockquote class='blockedit'>{{Box-round|title= | <blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}} | ||
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" />. | 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)== | ==Gene Mutations (SNV / INDEL)== | ||
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span> | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
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!Notes | !Notes | ||
|- | |- | ||
| | |EXAMPLE: TP53; Variable LOF mutations | ||
EXAMPLE: | |||
EGFR; Exon 20 mutations | EGFR; Exon 20 mutations | ||
EXAMPLE: BRAF; Activating mutations | |||
| | |EXAMPLE: TSG | ||
| | |EXAMPLE: 20% (COSMIC) | ||
EXAMPLE: 30% (add Reference) | |||
| | |EXAMPLE: IDH1 R123H | ||
| | |EXAMPLE: EGFR amplification | ||
| | | | ||
| | | | ||
| | | | ||
| | |EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference). | ||
<br /> | <br /> | ||
|} | |} | ||
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<blockquote class='blockedit'>{{Box-round|title= | <blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}} | ||
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" />. | 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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==Genes and Main Pathways Involved== | ==Genes and Main Pathways Involved== | ||
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span> | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome | !Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome | ||
|- | |- | ||
| | |EXAMPLE: BRAF and MAP2K1; Activating mutations | ||
| | |EXAMPLE: MAPK signaling | ||
| | |EXAMPLE: Increased cell growth and proliferation | ||
|- | |- | ||
| | |EXAMPLE: CDKN2A; Inactivating mutations | ||
| | |EXAMPLE: Cell cycle regulation | ||
| | |EXAMPLE: Unregulated cell division | ||
|- | |- | ||
| | |EXAMPLE: KMT2C and ARID1A; Inactivating mutations | ||
| | |EXAMPLE: Histone modification, chromatin remodeling | ||
| | |EXAMPLE: Abnormal gene expression program | ||
|} | |} | ||
<blockquote class='blockedit'>{{Box-round|title= | <blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}} | ||
'''JAK2''' | '''JAK2''' | ||