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HAEM5:T-prolymphocytic leukaemia (view source)

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[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]

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(''General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ HUGO-approved gene names and symbols] (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'' ''[[Author_Instructions]]'' ''and [[Frequently Asked Questions (FAQs)|FAQs]] as well as contact your [[Leadership|Associate Editor]] or [mailto:CCGA@cancergenomics.org Technical Support])''

==Primary Author(s)*==

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~~Put your text here~~ ~~(''EXAMPLE:'' Jane Smith, PhD)~~

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Parastou Tizro, MD

==WHO Classification of Disease==

(Will be autogenerated; Book will include name of specific book and have a link to the online WHO site)

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==Definition / Description of Disease==

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~~Put your text here ~~(~~''Instructions: Brief description~~ of ~~approximately one paragraph~~ - ~~include disease context relative~~ to ~~other WHO classification categories~~, ~~diagnostic criteria if applicable, and differential diagnosis if applicable~~. ~~Other classifications can be referenced for comparison.'') ~~

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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==

Put your text here (''Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.'')

==Epidemiology / Prevalence==

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~~Put your text here~~

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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==

Put your text here and fill in the table (''Instruction: Can include references in the table. Do not delete table.'')

{| class="wikitable"

|'''Signs and Symptoms'''

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|~~EXAMPLE: Asymptomatic~~ (~~incidental finding on complete blood counts~~)

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|Hepatosplenomegaly (Frequently observed)

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~~EXAMPLE: B-symptoms~~ (~~weight loss, fever, night sweats)~~

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Generalized lymphadenopathy with slightly enlarged lymph nodes (Frequently observed

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~~EXAMPLE: Lymphadenopathy~~ (~~uncommon~~)

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Cutaneous involvement (20%)

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Malignant effusions (15%)

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Asymptomatic and indolent phase (30% of cases)

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|'''Laboratory Findings'''

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|~~EXAMPLE: Cytopenias~~

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|Anaemia and thrombocytopenia

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~~~~EXAMPLE:<~~/~~span> Lymphocytosis~~ (~~low level)

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Marked lymphocytosis > 100 × 10^9/L (75% of cases)

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==Sites of Involvement==

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~~Put your text here (''Instruction: Indicate physical sites; EXAMPLE: nodal, extranodal~~, bone marrow~~'') ~~

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Peripheral blood, bone marrow, spleen, liver, lymph node, and sometimes skin and serosa

==Morphologic Features==

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~~Put your text here (''Instructions: Brief description~~ of ~~typically approximately one paragraph'') ~~

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Blood smears display anemia, thrombocytopenia, and leukocytosis, predominantly of atypical lymphocytes. Bone marrow aspirates show aggregates of neoplastic lymphoid cells.

==Immunophenotype==

Put your text here and fill in the table (''Instruction: Can include references in the table. Do not delete table.'')

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!Finding!!Marker

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|Positive (universal)||~~EXAMPLE: CD1~~

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|Positive (universal)||CD2, CD3 (may be weak), CD5, CD7

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|Positive (subset)||

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|Positive (subset)||CD4 (in some cases CD4+/CD8+ or CD4-/CD8+), CD52

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|Negative (universal)||

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|Negative (universal)||TdT, CD1a

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|Negative (subset)||

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|Negative (subset)||CD8 (in some cases CD4+/CD8+ or CD4-/CD8+)

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==Chromosomal Rearrangements (Gene Fusions)==

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!Notes

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|~~EXAMPLE:~~ t(9;22)(~~q34~~;~~q11.2~~)|~~|EXAMPLE: 3'ABL1~~ / ~~5'BCR~~||EXAMPLE: der(22)||EXAMPLE: 20% (COSMIC)

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|t(14;14)(q11;q32)

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|TCL1A/TRD||EXAMPLE: der(22)||EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add reference)

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|~~EXAMPLE:~~ Yes

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|Yes

|EXAMPLE: No

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|~~EXAMPLE:~~ Yes

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|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).

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|t(X;14)(q28;q11.2)

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|MTCP1/TRD

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|Low (5%)

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|Yes

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

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!Notes

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|<~~span class="blue-text">EXAMPLE:<~~/~~span~~>

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|Gain

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|~~EXAMPLE: Loss~~

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|idic(8)(p11.2)

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|~~EXAMPLE:~~

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~~chr7:1-159,335,973 [hg38]~~

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t(8;8)(p11.2;q12)

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|~~EXAMPLE:~~<~~/span~~>

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~~chr7~~

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trisomy 8q

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|~~EXAMPLE: Yes~~

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|chr8

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|~~EXAMPLE: Yes~~

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|No

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|~~EXAMPLE~~:</~~span> No~~

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|No

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|~~EXAMPLE:~~</~~span~~>

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|No

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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).

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|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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|~~EXAMPLE:~~

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8

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|~~EXAMPLE: Gain~~

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~~chr8:1-145,138,636 [hg38]~~

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~~chr8~~

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|~~EXAMPLE: No~~

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|~~EXAMPLE: No~~

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|~~EXAMPLE: No~~

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~~Common recurrent secondary finding for t(8;21) (add reference).~~

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==Characteristic Chromosomal Patterns==

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!Notes

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|~~EXAMPLE:~~

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|inv(14)(q11q32)

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~~Co-deletion of 1p and 18q~~

|EXAMPLE: Yes

|EXAMPLE: No

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|EXAMPLE: No

|EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).

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|TCL1A

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|Oncogene

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|ATM mutations

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|None specified

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|Yes

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|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.

==Epigenomic Alterations==

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|EXAMPLE: Increased cell growth and proliferation

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|~~EXAMPLE: ''CDKN2A''; Inactivating mutations~~

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|TCL1A

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|~~EXAMPLE: Cell cycle regulation~~

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|T-cell signaling

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|~~EXAMPLE: Unregulated~~ cell ~~division~~

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|Increased cell survival and proliferation

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|EXAMPLE: ''KMT2C'' and ''ARID1A''; Inactivating mutations

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==Genetic Diagnostic Testing Methods==

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~~Put your text here~~

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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==

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~~Put your text here~~ <~~span style~~=~~"color~~:~~#0070C0"~~>(~~''Instructions~~: ~~Include associated hereditary conditions~~/~~syndromes that cause this entity or are caused by this entity~~.~~'')~~ </~~span~~>

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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==

Put your text here

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<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.

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[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases T]]

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[[Category:HAEM5]]

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[[Category:DISEASE]]

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[[Category:Diseases T]]

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Parastou.Tizro

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