Changes

|Yes

|Yes

|Yes

|Yes

|Yes (poor  

|Yes (poor

|Frequent, '''Minor diagnostic criteria'''.<ref name=":6" />

|Frequent, '''Minor diagnostic criteria'''.<ref name=":6" />

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|-

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==Gene Mutations (SNV / INDEL)==

==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.  

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.  

Deletions and mutations of the ATM gene (present in up to 90% of T-PLL cases but typically absent in other mature T-cell malignancies) are considered highly indicative for a diagnosis of suspected TCL1 family-negative T-PLL.<ref name=":8">{{Cite journal|last=Schrader|first=A.|last2=Crispatzu|first2=G.|last3=Oberbeck|first3=S.|last4=Mayer|first4=P.|last5=Pützer|first5=S.|last6=von Jan|first6=J.|last7=Vasyutina|first7=E.|last8=Warner|first8=K.|last9=Weit|first9=N.|date=2018-02-15|title=Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions form the basis of T-PLL|url=https://pubmed.ncbi.nlm.nih.gov/29449575|journal=Nature Communications|volume=9|issue=1|pages=697|doi=10.1038/s41467-017-02688-6|issn=2041-1723|pmc=5814445|pmid=29449575}}</ref><ref name=":3" />

Deletions and mutations of the ATM gene (present in up to 90% of T-PLL cases but typically absent in other mature T-cell malignancies) are considered highly indicative for a diagnosis of suspected TCL1 family-negative T-PLL.<ref name=":8">{{Cite journal|last=Schrader|first=A.|last2=Crispatzu|first2=G.|last3=Oberbeck|first3=S.|last4=Mayer|first4=P.|last5=Pützer|first5=S.|last6=von Jan|first6=J.|last7=Vasyutina|first7=E.|last8=Warner|first8=K.|last9=Weit|first9=N.|date=2018-02-15|title=Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions form the basis of T-PLL|url=https://pubmed.ncbi.nlm.nih.gov/29449575|journal=Nature Communications|volume=9|issue=1|pages=697|doi=10.1038/s41467-017-02688-6|issn=2041-1723|pmc=5814445|pmid=29449575}}</ref><ref name=":3" />

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==Genetic Diagnostic Testing Methods==

==Genetic Diagnostic Testing Methods==

Diagnosing T-cell prolymphocytic leukemia (T-PLL) involves a combination of clinical evaluation, laboratory tests, and imaging studies as well as genetic testing:

Diagnosing T-PLL involves a combination of clinical evaluation, laboratory tests, imaging studies, and genetic testing to identify diagnostic criteria. T-cell clonality can be confirmed through PCR, NGS, or flow cytometry.<ref>{{Cite journal|last=Kotrova|first=Michaela|last2=Novakova|first2=Michaela|last3=Oberbeck|first3=Sebastian|last4=Mayer|first4=Petra|last5=Schrader|first5=Alexandra|last6=Knecht|first6=Henrik|last7=Hrusak|first7=Ondrej|last8=Herling|first8=Marco|last9=Brüggemann|first9=Monika|date=2018-11|title=Next-generation amplicon TRB locus sequencing can overcome limitations of flow-cytometric Vβ expression analysis and confirms clonality in all T-cell prolymphocytic leukemia cases|url=https://pubmed.ncbi.nlm.nih.gov/30414304|journal=Cytometry. Part A: The Journal of the International Society for Analytical Cytology|volume=93|issue=11|pages=1118–1124|doi=10.1002/cyto.a.23604|issn=1552-4930|pmid=30414304}}</ref> Patients with T-PLL often exhibit complex karyotypes with recurrent genetic features that aid in diagnosis. Therefore, cytogenetic studies are useful for distinguishing T-PLL from other T-lymphoproliferative disorders.<ref name=":6" />

'''Cytogenetic Analysis'''  

* '''Cytogenetic Analysis'''

Karyotyping: To identify characteristic chromosomal abnormalities, such as inv(14)(q11q32), t(14;14)(q11;q32), or other translocations involving chromosome 14.

# Karyotyping: To identify characteristic chromosomal abnormalities, such as inv(14)(q11q32), t(14;14)(q11;q32), or other translocations involving chromosome 14. '''Major diagnostic criteria'''

# Fluorescence In Situ Hybridization (FISH): To detect specific genetic abnormalities, such as TCL1 gene rearrangements as a '''Major diagnostic criterion''' or MYC as a '''Minor diagnostic criterion''' (alternatively, molecular studies could be used). see note.  

Fluorescence In Situ Hybridization (FISH): To detect specific genetic abnormalities, such as TCL1 gene rearrangements (alternatively, molecular studies could be used).

<small><u>'''Note:''' ''TCL1A'' break-apart probes specific to the 14q32 region can identify translocations involving TCL1A. When a ''TCL1A'' rearrangement is not identified and the patient has T-cell prolymphocytic leukemia/lymphoma (T-PLL), reflex testing using the ''TRAD'' break-apart probe set may be performed.</u></small>

'''Molecular Genetic Testing'''

* '''Molecular Genetic Testing'''

Polymerase Chain Reaction (PCR) and Reverse Transcription PCR (RT-PCR):  

# Polymerase Chain Reaction (PCR) and Reverse Transcription PCR (RT-PCR): To show the rearrangements of the TR gene (TCRB, TCRG loci) as a '''Major diagnostic criterion,''' and alternative to FISH rearrangements of the ''TCL1'' or ''MTCP'' genes at the ''TRD'' locus can be detected by PCR. '''Major diagnostic criteria'''  

 

# Next generation sequencing (NGS)-See note

 

To detect gene rearrangements at a molecular level

 

 

The genetic diagnostic process involves cytogenetic studies (CpG-stimulated Karyotype and FISH) in addition to PCR  detecting clonal rearrangements of the TR gene and rearrangements of the ''TCL1'' gene at the ''TRB'' or ''TRG'' loci by PCR. Although, the alterations of ''TCL1A, TCL1B'' (TML1), or ''MTCP'' (third major diagnostic criterion) is present in more than 90% of cases; however, it is not present in 100%, and therefore at least 1 of the less common genetic features or T-PLL typical site involvements has to be present, in this case Next-Generation Sequencing (NGS) may be helpful.

==Familial Forms==

==Familial Forms==

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>

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>