HAEM5:T-prolymphocytic leukaemia: Difference between revisions

{{DISPLAYTITLE:T-prolymphocytic leukaemia}}

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

==Primary Author(s)*==

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|No

|No

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

|No

|No

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

Table: A list of clinically significant and/or recurrent CNAs and CN-LOH with potential or strong diagnostic, prognostic and treatment implications in T-PLL are listed below.   

|No

|No

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|5

|Yes

|No

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|6

|Yes

|Yes (poor)

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|12

|No

|Haploinsufficiency of the ''CDKN1B'' gene at the 12p13 locus contributes to the development of T-PLL.<ref>{{Cite journal|last=Le Toriellec|first=Emilie|last2=Despouy|first2=Gilles|last3=Pierron|first3=Gaëlle|last4=Gaye|first4=Nogaye|last5=Joiner|first5=Marjorie|last6=Bellanger|first6=Dorine|last7=Vincent-Salomon|first7=Anne|last8=Stern|first8=Marc-Henri|date=2008-02-15|title=Haploinsufficiency of CDKN1B contributes to leukemogenesis in T-cell prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/18073348|journal=Blood|volume=111|issue=4|pages=2321–2328|doi=10.1182/blood-2007-06-095570|issn=0006-4971|pmid=18073348}}</ref>

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|13

|No

|No

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|17

|No

|Leading to the dysregulation of genes such as ''BCL11B'', which is crucial in T-cell development and function.<ref name=":0" />

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==Diagnostic criteria==

Diagnosis requires either <u>all three major criteria</u> '''or''' the <u>first two major criteria along with one minor criterion</u>:<ref name=":5" />

==Characteristic Chromosomal or Other Global Mutational Patterns==

[[File:Inv(14)(q11.2q32).png|thumb|Inv(14)(q11.2q32)]]

The most common chromosomal abnormality in T-PLL involves an inversion of chromosome 14, with breakpoints at q11.2 and q32.1, observed in about 60-80% of patients and described as inv(14). Additionally, in 10-20% of cases, there is a translocation t(14;14)(q11.2;q32.1).<ref name=":5" /> <ref name=":7" />

|The most common chromosomal abnormality in T-PLL involves an inversion of chromosome 14, with breakpoints at q11.2 and q32.1, observed in about 60-80% of patients and described as inv(14). Additionally, in 10-20% of cases, there is a translocation t(14;14)(q11.2;q32.1)

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==Gene Mutations (SNV/INDEL)==

Although gene mutations beyond ''TCL1'' family alterations are not yet recognized as diagnostic criteria and remain under investigation for T-PLL, the mutational landscape of T-PLL provides valuable insights. These discoveries open up potential avenues for novel targeted therapies in treating this aggressive form of leukemia.  

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!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

|Mutations in TP53 are less frequent than deletions.<ref name=":9" />May show overexpression of p53 in some cases.<ref name=":7" />

|}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==

Research indicates that epigenetic modifications in the regulatory regions of key oncogenes and genes involved in DNA damage response and T-cell receptor regulation are clearly present. These changes are closely associated with the transcriptional dysregulation that forms the core lesions of T-PLL.<ref>{{Cite journal|last=Tian|first=Shulan|last2=Zhang|first2=Henan|last3=Zhang|first3=Pan|last4=Kalmbach|first4=Michael|last5=Lee|first5=Jeong-Heon|last6=Ordog|first6=Tamas|last7=Hampel|first7=Paul J.|last8=Call|first8=Timothy G.|last9=Witzig|first9=Thomas E.|date=2021-04-15|title=Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/33859327|journal=Scientific Reports|volume=11|issue=1|pages=8318|doi=10.1038/s41598-021-87890-9|issn=2045-2322|pmc=8050249|pmid=33859327}}</ref>

While there is no noticeable familial clustering of T-cell prolymphocytic leukemia (T-PLL), a subset of cases can develop in the context of ataxia-telangiectasia (AT). AT is characterized by germline mutations in the ''ATM'' gene, and patients with AT are at an increased risk for various malignancies, including T-PLL. In these cases, biallelic inactivation of the ''ATM'' tumor suppressor gene occurs, with about 10% to 15% penetrance of the tumor phenotype by early adulthood. T-PLL represents nearly 3% of all malignancies in patients with ataxia-telangiectasia​. <ref>{{Cite journal|last=Suarez|first=Felipe|last2=Mahlaoui|first2=Nizar|last3=Canioni|first3=Danielle|last4=Andriamanga|first4=Chantal|last5=Dubois d'Enghien|first5=Catherine|last6=Brousse|first6=Nicole|last7=Jais|first7=Jean-Philippe|last8=Fischer|first8=Alain|last9=Hermine|first9=Olivier|date=2015-01-10|title=Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies|url=https://pubmed.ncbi.nlm.nih.gov/25488969|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=33|issue=2|pages=202–208|doi=10.1200/JCO.2014.56.5101|issn=1527-7755|pmid=25488969}}</ref> <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> <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==

==Links==

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