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{{DISPLAYTITLE:T-prolymphocytic leukaemia}}
{{DISPLAYTITLE:T-prolymphocytic leukaemia}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
{{Under Construction}}
{{Under Construction}}
<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); to add (or move) a row or column to a table, click nearby within the table and select the > symbol that appears to be given options. 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)*==
Parastou Tizro, MD<span style="color:#0070C0"> </span>
==WHO Classification of Disease==
<span style="color:#0070C0">(Will be autogenerated; Book will include name of specific book and have a link to the online WHO site)</span>
{| class="wikitable"
!Structure
!Disease
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|Family
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==Definition / Description of Disease==
==Definition / Description of Disease==
T-prolymphocytic leukemia (T-PLL) is an aggressive form of T-cell leukemia marked by the proliferation of small to medium-sized prolymphocytes exhibiting a mature post-thymic T-cell phenotype. This condition is characterized by the juxtaposition of TCL1A or MTCP1 genes to a TR locus, typically the TRA/TRD locus.
==Synonyms / Terminology==
==Synonyms / Terminology==
Put your text here <span style="color:#0070C0">(''Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.'') </span>
Put your text here <span style="color:#0070C0">(''Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.'') </span>
==Epidemiology / Prevalence==
==Epidemiology / Prevalence==
T-PLL is a rare disorder, comprising about 2% of all mature lymphoid leukemia cases in adults. It primarily occurs in the elderly, with a median age of 65 years (ranging from 30 to 94 years), and shows a slight male predominance with a male to female ratio of 1.33:1.
==Clinical Features==
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
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)
|Hepatosplenomegaly (Frequently observed)
Generalized lymphadenopathy with slightly enlarged lymph nodes (Frequently observed
Cutaneous involvement (20%)
Malignant effusions (15%)
Asymptomatic and indolent phase (30% of cases)
|-
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|'''Laboratory Findings'''
|'''Laboratory Findings'''
|EXAMPLE Cytopenias
|Anaemia and thrombocytopenia
Marked lymphocytosis > 100 × 10^9/L (75% of cases)
|}
|}
==Sites of Involvement==
==Sites of Involvement==
Peripheral blood, bone marrow, spleen, liver, lymph node, and sometimes skin and serosa
==Morphologic Features==
==Morphologic Features==
Blood smears display anemia, thrombocytopenia, and leukocytosis, predominantly of atypical lymphocytes. Bone marrow aspirates show aggregates of neoplastic lymphoid cells.
==Immunophenotype==
==Immunophenotype==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
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
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|Positive (universal)||EXAMPLE CD1
|Positive (universal)||CD2, CD3 (may be weak), CD5, CD7
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|Positive (subset)||EXAMPLE CD2
|Positive (subset)||CD4 (in some cases CD4+/CD8+ or CD4-/CD8+), CD52
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|Negative (universal)||EXAMPLE CD3
|Negative (universal)||TdT, CD1a
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|Negative (subset)||EXAMPLE CD4
|Negative (subset)||CD8 (in some cases CD4+/CD8+ or CD4-/CD8+)
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==Chromosomal Rearrangements (Gene Fusions)==
==Chromosomal Rearrangements (Gene Fusions)==
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{| class="wikitable sortable"
{| class="wikitable sortable"
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!Notes
!Notes
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|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
|t(14;14)(q11;q32)
EXAMPLE 30% (add reference)
|TCL1A/TRD||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
|Yes
|Yes
|No
|<span class="blue-text">EXAMPLE:</span> No
|Yes
|Yes
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span>
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).
|}
|-
|t(X;14)(q28;q11.2)
==Individual Region Genomic Gain/Loss/LOH==
|MTCP1/TRD
|
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>
|Low (5%)
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|Yes
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==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. Do not delete table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
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!Notes
!Notes
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|EXAMPLE
|8
|Gain
|idic(8)(p11.2)
|EXAMPLE Loss
|EXAMPLE
t(8;8)(p11.2;q12)
trisomy 8q<br />
|Yes
|chr8
|No
|No
|No
|No
|No
|No
|No
|Common recurrent secondary finding (70-80% of cases).<ref>{{Cite journal|last=Matutes|first=E.|last2=Brito-Babapulle|first2=V.|last3=Swansbury|first3=J.|last4=Ellis|first4=J.|last5=Morilla|first5=R.|last6=Dearden|first6=C.|last7=Sempere|first7=A.|last8=Catovsky|first8=D.|date=1991-12-15|title=Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/1742486|journal=Blood|volume=78|issue=12|pages=3269–3274|issn=0006-4971|pmid=1742486}}</ref>
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Common recurrent secondary finding for t(8;21) (add reference).
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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. Do not delete table.'')</span>
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"
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!Notes
!Notes
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|EXAMPLE
|inv(14)(q11q32)
|<span class="blue-text">EXAMPLE:</span> Yes
|<span class="blue-text">EXAMPLE:</span> No
|<span class="blue-text">EXAMPLE:</span> No
|No
|<span class="blue-text">EXAMPLE:</span>
|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).
|}
|}
==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 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. Do not delete table.'') </span>
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
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|EXAMPLE: TP53; Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
<span class="blue-text">EXAMPLE:</span>
''EGFR''; Exon 20 mutations
<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> TSG
EXAMPLE: BRAF; Activating mutations
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
|EXAMPLE: TSG
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
|EXAMPLE: 20% (COSMIC)
|<span class="blue-text">EXAMPLE:</span> ''IDH1'' R123H
|<span class="blue-text">EXAMPLE:</span> ''EGFR'' amplification
EXAMPLE: 30% (add Reference)
|<span class="blue-text">EXAMPLE:</span> Yes
|EXAMPLE: IDH1 R123H
|<span class="blue-text">EXAMPLE:</span> No
|EXAMPLE: EGFR amplification
|<span class="blue-text">EXAMPLE:</span> No
|<span class="blue-text">EXAMPLE:</span> Excludes hairy cell leukemia (HCL) (add reference).
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|TCL1A
|Oncogene
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|ATM mutations
|None specified
|Yes
|Yes
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|}Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
==Epigenomic Alterations==
==Epigenomic Alterations==
Put your text here
Put your text here
==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 table. Do not delete table.'')</span>
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"
|-
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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
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|EXAMPLE: BRAF and MAP2K1; Activating mutations
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|EXAMPLE: MAPK signaling
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
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|EXAMPLE: CDKN2A; Inactivating mutations
|TCL1A
|EXAMPLE: Cell cycle regulation
|T-cell signaling
|EXAMPLE: Unregulated cell division
|Increased cell survival and proliferation
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|EXAMPLE: KMT2C and ARID1A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|EXAMPLE: Histone modification, chromatin remodeling
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|EXAMPLE: Abnormal gene expression program
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
The genetic diagnostic process involves detecting clonal rearrangements of the TR gene and rearrangements of the TCL1 gene at the TRB or TRG loci.
==Familial Forms==
==Familial Forms==
A subset of cases may develop in the context of ataxia-telangiectasia (AT), which is characterized by germline mutations in the ATM gene. Penetrance of the tumor phenotype is about 10% to 15% by early adulthood.<ref>{{Cite journal|last=Taylor|first=A. M.|last2=Metcalfe|first2=J. A.|last3=Thick|first3=J.|last4=Mak|first4=Y. F.|date=1996-01-15|title=Leukemia and lymphoma in ataxia telangiectasia|url=https://pubmed.ncbi.nlm.nih.gov/8555463|journal=Blood|volume=87|issue=2|pages=423–438|issn=0006-4971|pmid=8555463}}</ref> It represents nearly 3% of all malignancies in patients with ataxia-telangiectasia.<ref>{{Cite journal|last=Li|first=Geling|last2=Waite|first2=Emily|last3=Wolfson|first3=Julie|date=2017-12-26|title=T-cell prolymphocytic leukemia in an adolescent with ataxia-telangiectasia: novel approach with a JAK3 inhibitor (tofacitinib)|url=https://pubmed.ncbi.nlm.nih.gov/29296924|journal=Blood Advances|volume=1|issue=27|pages=2724–2728|doi=10.1182/bloodadvances.2017010470|issn=2473-9529|pmc=5745136|pmid=29296924}}</ref>
==Additional Information==
==Additional Information==
Put your text here
Put your text here
==Links==
==Links==
(use the "Link" icon that looks like two overlapping circles at the top of the page) <span style="color:#0070C0">(''Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
==References==
==References==
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(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span>
==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases T]]
<references />