Compendium of Cancer Genome Aberrations

HAEM5:T-prolymphocytic leukaemia: Difference between revisions

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{{DISPLAYTITLE:T-prolymphocytic leukaemia}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
==Primary Author(s)*==
==Primary Author(s)*==
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{| class="wikitable"
{| class="wikitable"
|+
|Acceptable
|Acceptable
|N/A
|N/A
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==Gene Rearrangements==
==Gene Rearrangements==
Rearrangements involving the TCL1 (T-cell leukemia/lymphoma 1) family genes—''TCL1A, MTCP1'' (mature T-cell proliferation), or ''TCL1B'' (also known as ''TCL1/MTCP''1-like 1 [''TML''1])—are highly specific to T-PLL and occur in more than 90% of cases. These translocations juxtapose the ''TRA'' locus with the oncogenes ''TCL1A'' or ''TCL1B'', or in the case of t(X;14), with the ''MTCP1'' gene.<ref name=":6" /><ref name=":7">Matutes E, et al., (2017). T-cell prolymphocytic leukemia, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France, p346-347.</ref>
Rearrangements involving the TCL1 (T-cell leukemia/lymphoma 1) family genes—''TCL1A, MTCP1'' (mature T-cell proliferation), or ''TCL1B'' (also known as ''TCL1/MTCP''1-like 1 [''TML''1])—are highly specific to T-PLL and occur in more than 90% of cases. These translocations juxtapose the ''TRA'' locus with the oncogenes ''TCL1A'' or ''TCL1B'', or in the case of t(X;14), with the ''MTCP1'' gene.<ref name=":6">{{Cite journal|last=Staber|first=Philipp B.|last2=Herling|first2=Marco|last3=Bellido|first3=Mar|last4=Jacobsen|first4=Eric D.|last5=Davids|first5=Matthew S.|last6=Kadia|first6=Tapan Mahendra|last7=Shustov|first7=Andrei|last8=Tournilhac|first8=Olivier|last9=Bachy|first9=Emmanuel|date=2019-10-03|title=Consensus criteria for diagnosis, staging, and treatment response assessment of T-cell prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/31292114|journal=Blood|volume=134|issue=14|pages=1132–1143|doi=10.1182/blood.2019000402|issn=1528-0020|pmc=7042666|pmid=31292114}}</ref><ref name=":7">Matutes E, et al., (2017). T-cell prolymphocytic leukemia, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France, p346-347.</ref>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Driver Gene!!Fusion(s) and Common Partner Genes!!''Molecular Pathogenesis''!!Typical Chromosomal Alteration(s)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
Line 49: Line 46:
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|inv(14)<br />||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||t(14;14)(q11.2;q32.1)
|inv(14)<br />||TCRα/δ and TCL1A||Pericentric inversion within chromosome 14, leading to '''j'''uxtaposition of the ''TCRα/δ'' enhancer to the ''TCL1A'' locus and aberrant overexpression of ''TCL1A''||inv(14)(q11.2q32.1)*
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|Common ~60%
|<span class="blue-text">EXAMPLE:</span> D, P, T
|D
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|No
|<span class="blue-text">EXAMPLE:</span>
|These genetic abnormalities serve as diagnostic markers and generally indicate an aggressive disease. Major diagnostic criteria.<ref name=":6" />
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). BCR::ABL1 is generally favorable in CML (add reference).
|-
|t(X;14)
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|t(X;14)(q28;q11.2)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
|
|<span class="blue-text">EXAMPLE:</span>
 
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
 
 
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|<span class="blue-text">EXAMPLE:</span>
 
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|t(14;14)
|<span class="blue-text">EXAMPLE:</span> N/A
|TCRα/δ and TCL1A
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|''Reciprocal translocation between the two'' homologous chromosome 14s, leading to juxtaposition of the ''TCRα/δ'' enhancer to the ''TCL1A'' locus  and aberrant overexpression of ''TCL1A''
|<span class="blue-text">EXAMPLE:</span> N/A
|t(14;14)(q11.2;q32.1)*
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|Recurrent ~20-25%
|<span class="blue-text">EXAMPLE:</span> D, P, T
|D
|
|
|-
|
|
|
|
|
|
|
|
|}
 
<br />
{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|inv(14)(q11.2q32.1)
t(14;14)(q11.2;q32.1)
|''TCL1A/B ,TRD''|| ||inv(14) ~60%
t(14;14) ~25%
|Yes
|No
|No
|No
|These genetic abnormalities serve as diagnostic markers and generally indicate an aggressive disease. This is due to their role in overexpressing oncogenes like ''TCL1A''. Major diagnostic criteria.<ref name=":6" />
|*In most diagnostic/genetic reports (e.g., FISH or karyotype), the inversion and translocation may grouped together. Their distinction is mainly cytogenetic, not biological.
|-
|-
|t(X;14)
|''TCRα/δ and MTCP1''
|Transcriptional activation of ''MTCP1'' via juxtaposition to ''TCRα/δ'' enhancer elements, leading to ''AKT'' pathway activation
|t(X;14)(q28;q11.2)
|t(X;14)(q28;q11.2)
|''MTCP1, TRD''
|Rare ~5%
|
|D
|Low (5%)
|Yes
|No
|No
|No
|Major diagnostic criteria.<ref name=":6" />
|Major diagnostic criteria.<ref name=":6" /> Rarely, t(X;7)(q28;q34) is observed, where the TCRβ enhancer (7q34) substitutes for TCRα/δ, leading to the same functional outcome
|}
|}
==Individual Region Genomic Gain/Loss/LOH==
Approximately 70-80% of T-PLL karyotypes are complex, which is considered minor diagnostic criteria, and usually include 3-5 or more structural aberrations. Common cytogenetic abnormalities include those of chromosome 8, such as idic(8)(p11.2), t(8;8)(p11.2;q12), and trisomy 8q. Other frequent changes are deletions in 12p13 and 22q, gains in 8q24 (MYC), and abnormalities in chromosomes 5p, 6, and 17.<ref name=":5">Elenitoba-Johnson K, et al. T-prolymphocytic leukemia. In: WHO Classification of Tumours Editorial Board. Haematolymphoid tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2024 [cited 2024 June 12]. (WHO classification of tumors series, 5th ed.; vol. 11). Available from: https://tumourclassification.iarc.who.int/chaptercontent/63/209</ref>


==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.
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span>
7
|<span class="blue-text">EXAMPLE:</span> Loss
|<span class="blue-text">EXAMPLE:</span>
chr7
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|<span class="blue-text">EXAMPLE:</span> No
|<span class="blue-text">EXAMPLE:</span>
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 references).
|-
|<span class="blue-text">EXAMPLE:</span>
8
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span>
chr8
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
17
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
''ERBB2''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|<span class="blue-text">EXAMPLE:</span>
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
|-
|
|
|
|
|
|
|
|}
Approximately 70-80% of T-PLL karyotypes are complex, which is considered minor diagnostic criteria, and usually include 3-5 or more structural aberrations. Common cytogenetic abnormalities include those of chromosome 8, such as idic(8)(p11.2), t(8;8)(p11.2;q12), and trisomy 8q. Other frequent changes are deletions in 12p13 and 22q, gains in 8q24 (MYC), and abnormalities in chromosomes 5p, 6, and 17.<ref name=":5">Elenitoba-Johnson K, et al. T-prolymphocytic leukemia. In: WHO Classification of Tumours Editorial Board. Haematolymphoid tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2024 [cited 2024 June 12]. (WHO classification of tumors series, 5th ed.; vol. 11). Available from: https://tumourclassification.iarc.who.int/chaptercontent/63/209</ref>
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. 
{| class="wikitable sortable"
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|-
|8
|8
|Gain
|Gain
|idic(8)(p11)
t(8;8)(p11;q12)
trisomy 8q<br />8q24 (''MYC'')
|idic(8)(p11.2)
|idic(8)(p11.2)
t(8;8)(p11.2;q12)
t(8;8)(p11.2;q12)


trisomy 8q<br />8q24 (''MYC'')
trisomy 8q<br />8q24  
|Yes
|''AGO2'' <ref name=":5" />'', MYC''
|No
|D
|No
|No
|Recurrent secondary finding (70-80% of cases). Minor diagnostic criteria.<ref name=":6">{{Cite journal|last=Staber|first=Philipp B.|last2=Herling|first2=Marco|last3=Bellido|first3=Mar|last4=Jacobsen|first4=Eric D.|last5=Davids|first5=Matthew S.|last6=Kadia|first6=Tapan Mahendra|last7=Shustov|first7=Andrei|last8=Tournilhac|first8=Olivier|last9=Bachy|first9=Emmanuel|date=2019-10-03|title=Consensus criteria for diagnosis, staging, and treatment response assessment of T-cell prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/31292114|journal=Blood|volume=134|issue=14|pages=1132–1143|doi=10.1182/blood.2019000402|issn=1528-0020|pmc=7042666|pmid=31292114}}</ref>
|Recurrent secondary finding (70-80% of cases). Minor diagnostic criteria.<ref name=":6" />
|-
|-
|5
|5
|Abnormality
|Abnormality
|5p, 5q <ref>{{Cite journal|last=Tirado|first=Carlos A.|last2=Starshak|first2=Phillip|last3=Delgado|first3=Paul|last4=Rao|first4=Nagesh|date=2012-08-20|title="T-cell prolymphocytic leukemia (T-PLL), a heterogeneous disease exemplified by two cases and the important role of cytogenetics: a multidisciplinary approach"|url=https://pubmed.ncbi.nlm.nih.gov/23211026|journal=Experimental Hematology & Oncology|volume=1|issue=1|pages=21|doi=10.1186/2162-3619-1-21|issn=2162-3619|pmc=3514161|pmid=23211026}}</ref>
|5p, 5q <ref>{{Cite journal|last=Tirado|first=Carlos A.|last2=Starshak|first2=Phillip|last3=Delgado|first3=Paul|last4=Rao|first4=Nagesh|date=2012-08-20|title="T-cell prolymphocytic leukemia (T-PLL), a heterogeneous disease exemplified by two cases and the important role of cytogenetics: a multidisciplinary approach"|url=https://pubmed.ncbi.nlm.nih.gov/23211026|journal=Experimental Hematology & Oncology|volume=1|issue=1|pages=21|doi=10.1186/2162-3619-1-21|issn=2162-3619|pmc=3514161|pmid=23211026}}</ref>
|
|Unknown
|Yes
|D, P
|Yes
|No
|No
|Minor diagnostic criteria.<ref name=":6" />
|Minor diagnostic criteria.<ref name=":6" />
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|6
|6
|Abnormality
|Abnormality
|gain of 6p, loss of 6q <ref>{{Cite journal|last=Dearden|first=Claire|date=2012-07-19|title=How I treat prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/22649104|journal=Blood|volume=120|issue=3|pages=538–551|doi=10.1182/blood-2012-01-380139|issn=1528-0020|pmid=22649104}}</ref><ref>{{Cite journal|last=Soulier|first=J.|last2=Pierron|first2=G.|last3=Vecchione|first3=D.|last4=Garand|first4=R.|last5=Brizard|first5=F.|last6=Sigaux|first6=F.|last7=Stern|first7=M. H.|last8=Aurias|first8=A.|date=2001-07|title=A complex pattern of recurrent chromosomal losses and gains in T-cell prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/11391795|journal=Genes, Chromosomes & Cancer|volume=31|issue=3|pages=248–254|doi=10.1002/gcc.1141|issn=1045-2257|pmid=11391795}}</ref>
|Gain of 6p, loss of 6q <ref>{{Cite journal|last=Dearden|first=Claire|date=2012-07-19|title=How I treat prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/22649104|journal=Blood|volume=120|issue=3|pages=538–551|doi=10.1182/blood-2012-01-380139|issn=1528-0020|pmid=22649104}}</ref><ref>{{Cite journal|last=Soulier|first=J.|last2=Pierron|first2=G.|last3=Vecchione|first3=D.|last4=Garand|first4=R.|last5=Brizard|first5=F.|last6=Sigaux|first6=F.|last7=Stern|first7=M. H.|last8=Aurias|first8=A.|date=2001-07|title=A complex pattern of recurrent chromosomal losses and gains in T-cell prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/11391795|journal=Genes, Chromosomes & Cancer|volume=31|issue=3|pages=248–254|doi=10.1002/gcc.1141|issn=1045-2257|pmid=11391795}}</ref>
|
|Unknown
|No
|Unknown
|No
|No
|No
|
|
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|11
|11
|Loss
|Loss
|11q
|11q21-q23.3
|ch11q21-q23.3
|''ATM''
|Yes
|D, P, T
|Yes
|No
|Yes (poor)
|Frequent, Minor diagnostic criteria.<ref name=":6" />PARP inhibitors may be considered as an off-label therapy (NCT03263637)
|Frequent, Minor diagnostic criteria.<ref name=":6" />
|-
|-
|12
|12
|Loss
|Loss
|12p
|12p13
|12p13
|Yes
|''CDKN1B''
|Yes
|D, P
|No
|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>
|Haploinsufficiency of the ''CDKN1B'' gene 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>Minor diagnostic criteria.<ref name=":6" />
Minor diagnostic criteria.<ref name=":6" />
|-
|-
|13
|13
|Loss
|Loss
|13q
|13q14.3
|13q14.3
|Yes
|
|No
|D
|No
|No
|Minor diagnostic criteria.<ref name=":6" />
|Minor diagnostic criteria.<ref name=":6" />
Line 258: Line 134:
|17
|17
|Loss
|Loss
|17p
|17p13
|17p13
|''TP53'' <ref name=":7" />
|P,T
|No
|No
|Yes
|May portend resistance to therapy
|Yes (resistance to therapy)
|May include ''TP53'' gene at 17p13.1 <ref name=":7" />
|-
|-
|22
|22
|Loss
|Loss
|Monosomy 22
|Monosomy 22
del(22q)
del(22q); 22q11-12 <ref>{{Cite journal|last=Stengel|first=Anna|last2=Kern|first2=Wolfgang|last3=Zenger|first3=Melanie|last4=Perglerová|first4=Karolina|last5=Schnittger|first5=Susanne|last6=Haferlach|first6=Torsten|last7=Haferlach|first7=Claudia|date=2014-12-06|title=A Comprehensive Cytogenetic and Molecular Genetic Characterization of Patients with T-PLL Revealed Two Distinct Genetic Subgroups and JAK3 Mutations As an Important Prognostic Marker|url=https://doi.org/10.1182/blood.V124.21.1639.1639|journal=Blood|volume=124|issue=21|pages=1639–1639|doi=10.1182/blood.v124.21.1639.1639|issn=0006-4971}}</ref><ref name=":0">{{Cite journal|last=Fang|first=Hong|last2=Beird|first2=Hannah C.|last3=Wang|first3=Sa A.|last4=Ibrahim|first4=Andrew F.|last5=Tang|first5=Zhenya|last6=Tang|first6=Guilin|last7=You|first7=M. James|last8=Hu|first8=Shimin|last9=Xu|first9=Jie|date=2023-09|title=T-prolymphocytic leukemia: TCL1 or MTCP1 rearrangement is not mandatory to establish diagnosis|url=https://pubmed.ncbi.nlm.nih.gov/37443196|journal=Leukemia|volume=37|issue=9|pages=1919–1921|doi=10.1038/s41375-023-01956-3|issn=1476-5551|pmid=37443196}}</ref> (most common)
|
|''BCL11B'' <ref name=":0" />
22q11-12 <ref>{{Cite journal|last=Stengel|first=Anna|last2=Kern|first2=Wolfgang|last3=Zenger|first3=Melanie|last4=Perglerová|first4=Karolina|last5=Schnittger|first5=Susanne|last6=Haferlach|first6=Torsten|last7=Haferlach|first7=Claudia|date=2014-12-06|title=A Comprehensive Cytogenetic and Molecular Genetic Characterization of Patients with T-PLL Revealed Two Distinct Genetic Subgroups and JAK3 Mutations As an Important Prognostic Marker|url=https://doi.org/10.1182/blood.V124.21.1639.1639|journal=Blood|volume=124|issue=21|pages=1639–1639|doi=10.1182/blood.v124.21.1639.1639|issn=0006-4971}}</ref><ref name=":0">{{Cite journal|last=Fang|first=Hong|last2=Beird|first2=Hannah C.|last3=Wang|first3=Sa A.|last4=Ibrahim|first4=Andrew F.|last5=Tang|first5=Zhenya|last6=Tang|first6=Guilin|last7=You|first7=M. James|last8=Hu|first8=Shimin|last9=Xu|first9=Jie|date=2023-09|title=T-prolymphocytic leukemia: TCL1 or MTCP1 rearrangement is not mandatory to establish diagnosis|url=https://pubmed.ncbi.nlm.nih.gov/37443196|journal=Leukemia|volume=37|issue=9|pages=1919–1921|doi=10.1038/s41375-023-01956-3|issn=1476-5551|pmid=37443196}}</ref>
|D
 
(most common)
|Yes
|No
|No
|No
|Minor diagnostic criteria.<ref name=":6" />
|Leading to the dysregulation of genes such as ''BCL11B'', which is crucial in T-cell development and function.<ref name=":0" />
Minor diagnostic criteria.<ref name=":6" />
|}
|}
==Diagnostic criteria==
==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" />
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" />
Line 296: Line 165:


==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as 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; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
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" />[[File:Inv(14)(q11.2q32).png|thumb|Inv(14)(q11.2q32)|alt=|center]]
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span>
Co-deletion of 1p and 18q
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|<span class="blue-text">EXAMPLE:</span> D, P
|
|
|-
|<span class="blue-text">EXAMPLE:</span>
Microsatellite instability - hypermutated
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
|-
|
|
|
|
|
|
|}
[[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" />
{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|-
|inv(14)(q11q32)
|inv(14)(q11q32)
t(14;14)(q11.2;q32.1)
t(14;14)(q11.2;q32.1)
|Yes
|''TCL1A'' or ''MTCP1'' activation with constitutive activation of the ''AKT'' signaling pathway, promoting proliferation and survival
|Common
|D
|No
|No
|Major diagnostic criteria <ref name=":6" />
|-
|ATM loss/mutation; del(11)(q22–q23)
|Impaired DNA damage response → genomic instability, accumulation of secondary lesions
|Common
|D,P
|No
|No
|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)
|Minor diagnostic criteria, the most frequent cooperating lesion <ref name=":6" />
|}
|}
==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 or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries 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. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
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.
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
Line 359: Line 201:
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|''ATM''


<br />
<br />
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|Mutation/deletion, loss of heterozygosity, or biallelic mutation
|<span class="blue-text">EXAMPLE:</span> Oncogene
|Tumor Suppressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|Common
|<span class="blue-text">EXAMPLE:</span> T
|D, P, T
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|No
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
|Since alterations at the ''ATM'' locus are found in up to 80% to 90% of T-PLL cases, it can serve as a minor diagnostic criterion.<ref name=":6" /><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>
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> P
|
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|
|-
|
|
|
|
|
|
|
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.


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" /><ref name=":3">{{Cite journal|last=Kiel|first=Mark J.|last2=Velusamy|first2=Thirunavukkarasu|last3=Rolland|first3=Delphine|last4=Sahasrabuddhe|first4=Anagh A.|last5=Chung|first5=Fuzon|last6=Bailey|first6=Nathanael G.|last7=Schrader|first7=Alexandra|last8=Li|first8=Bo|last9=Li|first9=Jun Z.|date=2014-08-28|title=Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/24825865|journal=Blood|volume=124|issue=9|pages=1460–1472|doi=10.1182/blood-2014-03-559542|issn=1528-0020|pmc=4148768|pmid=24825865}}</ref>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)!!Prevalence (COSMIC /  TCGA / Other)!!Concomitant Mutations!!Mutually Exclusive Mutations
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|''ATM''
|TSG
|53% (COSMIC)
|''ATM'' mutation/deletion
|None specified
|Yes
|Yes
|Yes (PARP inhibitors, NCT03263637)
|Since deletions of or missense mutations at the ''ATM'' locus are found in up to 80% to 90% of T-PLL cases, ''ATM'' alterations can serve as a minor diagnostic criterion.<ref name=":6" /><ref name=":8" />
|-
|-
|''FBXW10''
|''FBXW10''
|TSG
<br />
|72% (COSMIC)
|Loss-of-function
|''JAK/STAT'' pathway
|Tumor Supressor Gene
|None specified
|Common
|Unknown
|Unknown
|Unknown
|Unknown
|No
|
|
|-
|-
|''IL2RG,'' ''JAK1, JAK3, STAT5B''
|''IL2RG,'' ''JAK1, JAK3, STAT5B''
|Variable activating mutations
|Oncogene
|Oncogene
|8% ''JAK1''
|Variable based on gene; Recurrent to Common
 
|D, P, T
34% ''JAK3''
|No
 
|Targeting this pathway with specific ''JAK/STAT'' pathway inhibitors, has shown promise in preclinical studies and early clinical trials. Combining JAK/STAT inhibitors with other treatments, like BCL-2 inhibitors, may enhance therapeutic efficacy and improve outcomes for T-PLL patients <ref>{{Cite journal|last=Gomez-Arteaga|first=Alexandra|last2=Margolskee|first2=Elizabeth|last3=Wei|first3=Mike T.|last4=van Besien|first4=Koen|last5=Inghirami|first5=Giorgio|last6=Horwitz|first6=Steven|date=2019-07|title=Combined use of tofacitinib (pan-JAK inhibitor) and ruxolitinib (a JAK1/2 inhibitor) for refractory T-cell prolymphocytic leukemia (T-PLL) with a JAK3 mutation|url=https://pubmed.ncbi.nlm.nih.gov/30997845|journal=Leukemia & Lymphoma|volume=60|issue=7|pages=1626–1631|doi=10.1080/10428194.2019.1594220|issn=1029-2403|pmc=8162842|pmid=30997845}}</ref><ref>{{Cite journal|url=https://ashpublications.org/blood/article/126/23/5486/134544/Refractory-TCell-Prolymphocytic-Leukemia-with-JAK3|doi=10.1182/blood.v126.23.5486.5486}}</ref>
16% ''STAT5B''
 
2% ''IL2RG''
 
(COSMIC)
 
(cumulative prevalence of ~ 60%)<ref>{{Cite journal|last=Wahnschaffe|first=Linus|last2=Braun|first2=Till|last3=Timonen|first3=Sanna|last4=Giri|first4=Anil K.|last5=Schrader|first5=Alexandra|last6=Wagle|first6=Prerana|last7=Almusa|first7=Henrikki|last8=Johansson|first8=Patricia|last9=Bellanger|first9=Dorine|date=2019-11-21|title=JAK/STAT-Activating Genomic Alterations Are a Hallmark of T-PLL|url=https://pubmed.ncbi.nlm.nih.gov/31766351|journal=Cancers|volume=11|issue=12|pages=1833|doi=10.3390/cancers11121833|issn=2072-6694|pmc=6966610|pmid=31766351}}</ref>
|''ATM, TP53'', Epigenetic modifiers <ref name=":1">{{Cite journal|last=Andersson|first=E. I.|last2=Pützer|first2=S.|last3=Yadav|first3=B.|last4=Dufva|first4=O.|last5=Khan|first5=S.|last6=He|first6=L.|last7=Sellner|first7=L.|last8=Schrader|first8=A.|last9=Crispatzu|first9=G.|date=2018-03|title=Discovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling|url=https://pubmed.ncbi.nlm.nih.gov/28804127|journal=Leukemia|volume=32|issue=3|pages=774–787|doi=10.1038/leu.2017.252|issn=1476-5551|pmid=28804127}}</ref><ref name=":2">{{Cite journal|last=Pinter-Brown|first=Lauren C.|date=2021-12-30|title=JAK/STAT: a pathway through the maze of PTCL?|url=https://doi.org/10.1182/blood.2021014238|journal=Blood|volume=138|issue=26|pages=2747–2748|doi=10.1182/blood.2021014238|issn=0006-4971}}</ref>
|Typically, mutations within this pathway occur in a mutually exclusive manner.<ref name=":3">{{Cite journal|last=Kiel|first=Mark J.|last2=Velusamy|first2=Thirunavukkarasu|last3=Rolland|first3=Delphine|last4=Sahasrabuddhe|first4=Anagh A.|last5=Chung|first5=Fuzon|last6=Bailey|first6=Nathanael G.|last7=Schrader|first7=Alexandra|last8=Li|first8=Bo|last9=Li|first9=Jun Z.|date=2014-08-28|title=Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/24825865|journal=Blood|volume=124|issue=9|pages=1460–1472|doi=10.1182/blood-2014-03-559542|issn=1528-0020|pmc=4148768|pmid=24825865}}</ref>
|Yes
|Yes
|Yes
|Targeting this pathway with specific ''JAK/STAT'' pathway inhibitors, such as tofacitinib, has shown promise in preclinical studies and early clinical trials. Combining JAK/STAT inhibitors with other treatments, like BCL-2 inhibitors, may enhance therapeutic efficacy and improve outcomes for T-PLL patients<ref>{{Cite journal|last=Gomez-Arteaga|first=Alexandra|last2=Margolskee|first2=Elizabeth|last3=Wei|first3=Mike T.|last4=van Besien|first4=Koen|last5=Inghirami|first5=Giorgio|last6=Horwitz|first6=Steven|date=2019-07|title=Combined use of tofacitinib (pan-JAK inhibitor) and ruxolitinib (a JAK1/2 inhibitor) for refractory T-cell prolymphocytic leukemia (T-PLL) with a JAK3 mutation|url=https://pubmed.ncbi.nlm.nih.gov/30997845|journal=Leukemia & Lymphoma|volume=60|issue=7|pages=1626–1631|doi=10.1080/10428194.2019.1594220|issn=1029-2403|pmc=8162842|pmid=30997845}}</ref><ref>{{Cite journal|url=https://ashpublications.org/blood/article/126/23/5486/134544/Refractory-TCell-Prolymphocytic-Leukemia-with-JAK3|doi=10.1182/blood.v126.23.5486.5486}}</ref>
|-
|-
|''EZH2''
|''EZH2''
|Both oncogene and TSG
|Loss-of-function
|16% (COSMIC)
|Both oncogene and Tumor Suppressor Gene
|''JAK/STAT'' pathway<ref name=":1" /><ref name=":2" />
|Recurrent
|None specified
|Unknown
|No
|No
|No (see note)
|''EZH2'' inhibitors like tazemetostat have shown efficacy in other hematologic malignancies, providing a rationale for off-label use in T-PLL
|See note
|''EZH2'' inhibitors like tazemetostat have shown efficacy in other hematologic malignancies, providing a rationale for their potential use in T-PLL
|-
|-
|''BCOR''
|''BCOR''
|TSG
|Loss-of-function
|8% (COSMIC)
|Tumor Supressor Gene
|''JAK/STAT'' pathway<ref name=":1" /><ref name=":2" />
|Rare
|None specified
|Unknown
|No
|No (see note)
|No
|No
|A negative impact on overall survival (OS) was not observed for T-PLL patients in the study. However, this might be attributable to the relatively low number of cases compared to studies on AML and MDS.<ref name=":9">{{Cite journal|last=Stengel|first=Anna|last2=Kern|first2=Wolfgang|last3=Zenger|first3=Melanie|last4=Perglerová|first4=Karolína|last5=Schnittger|first5=Susanne|last6=Haferlach|first6=Torsten|last7=Haferlach|first7=Claudia|date=2016-01|title=Genetic characterization of T-PLL reveals two major biologic subgroups and JAK3 mutations as prognostic marker|url=https://pubmed.ncbi.nlm.nih.gov/26493028|journal=Genes, Chromosomes & Cancer|volume=55|issue=1|pages=82–94|doi=10.1002/gcc.22313|issn=1098-2264|pmid=26493028}}</ref>
|A negative impact on overall survival (OS) was not observed for T-PLL patients in the study. However, this might be attributable to the relatively low number of cases compared to studies on AML and MDS.<ref name=":9">{{Cite journal|last=Stengel|first=Anna|last2=Kern|first2=Wolfgang|last3=Zenger|first3=Melanie|last4=Perglerová|first4=Karolína|last5=Schnittger|first5=Susanne|last6=Haferlach|first6=Torsten|last7=Haferlach|first7=Claudia|date=2016-01|title=Genetic characterization of T-PLL reveals two major biologic subgroups and JAK3 mutations as prognostic marker|url=https://pubmed.ncbi.nlm.nih.gov/26493028|journal=Genes, Chromosomes & Cancer|volume=55|issue=1|pages=82–94|doi=10.1002/gcc.22313|issn=1098-2264|pmid=26493028}}</ref>
|-
|-
|''SAMHD1''
|''SAMHD1''
|TSG
|Loss-of-function
|~7-20%<ref name=":8" /><ref name=":4">{{Cite journal|last=Johansson|first=Patricia|last2=Klein-Hitpass|first2=Ludger|last3=Choidas|first3=Axel|last4=Habenberger|first4=Peter|last5=Mahboubi|first5=Bijan|last6=Kim|first6=Baek|last7=Bergmann|first7=Anke|last8=Scholtysik|first8=René|last9=Brauser|first9=Martina|date=2018-01-19|title=SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/29352181|journal=Blood Cancer Journal|volume=8|issue=1|pages=11|doi=10.1038/s41408-017-0036-5|issn=2044-5385|pmc=5802577|pmid=29352181}}</ref>
|Tumor Supressor Gene
|None specified
|Recurrent
|None specified
|D, P
|Yes
|Yes
|No
|No
|''SAMHD1'' mutations may indicate a defective DNA damage response and aggressive disease <ref name=":4" />
|''SAMHD1'' mutations may indicate a defective DNA damage response and aggressive disease <ref name=":4">{{Cite journal|last=Johansson|first=Patricia|last2=Klein-Hitpass|first2=Ludger|last3=Choidas|first3=Axel|last4=Habenberger|first4=Peter|last5=Mahboubi|first5=Bijan|last6=Kim|first6=Baek|last7=Bergmann|first7=Anke|last8=Scholtysik|first8=René|last9=Brauser|first9=Martina|date=2018-01-19|title=SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/29352181|journal=Blood Cancer Journal|volume=8|issue=1|pages=11|doi=10.1038/s41408-017-0036-5|issn=2044-5385|pmc=5802577|pmid=29352181}}</ref>
|-
|-
|''CHEK2''
|''CHEK2''
|TSG
|Loss-of-function
|5% (COSMIC)
|Tumor Supressor Gene
|''ATM, TP53, JAK/STA''T pathway, Epigenetic modifiers
|Rare
|None specified
|Unknown
|No
|Yes
|No
|No
|''CHEK2'' mutations may indicate a defective DNA damage response and aggressive disease <ref name=":3" /><ref>{{Cite journal|last=Braun|first=Till|last2=Dechow|first2=Annika|last3=Friedrich|first3=Gregor|last4=Seifert|first4=Michael|last5=Stachelscheid|first5=Johanna|last6=Herling|first6=Marco|date=2021|title=Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact|url=https://pubmed.ncbi.nlm.nih.gov/34869023|journal=Frontiers in Oncology|volume=11|pages=775363|doi=10.3389/fonc.2021.775363|issn=2234-943X|pmc=8639578|pmid=34869023}}</ref>
|''CHEK2'' mutations may indicate a defective DNA damage response and aggressive disease <ref name=":3" /><ref>{{Cite journal|last=Braun|first=Till|last2=Dechow|first2=Annika|last3=Friedrich|first3=Gregor|last4=Seifert|first4=Michael|last5=Stachelscheid|first5=Johanna|last6=Herling|first6=Marco|date=2021|title=Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact|url=https://pubmed.ncbi.nlm.nih.gov/34869023|journal=Frontiers in Oncology|volume=11|pages=775363|doi=10.3389/fonc.2021.775363|issn=2234-943X|pmc=8639578|pmid=34869023}}</ref>
|-
|-
|''TP53''
|''TP53''
|TSG
|Variable inactivating/loss of function mutations
|2% (COSMIC)
|Tumor Supressor Gene
|''ATM, JAK/STA''T pathway, Epigenetic modifiers
|Rare
|None specified-In a study of T-PLL case, TP53 mutations were predominantly found in patients lacking TCRA/D rearrangements.<ref name=":9" />
|P (may portend resistance to therapy)
|No
|No
|Yes
|Associated with resistance to therapy
|Mutations in TP53 are less frequent than deletions.<ref name=":9" />May show overexpression of p53 in some cases.<ref name=":7" />
|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.
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.


==Epigenomic Alterations==
==Epigenomic Alterations==
Line 589: Line 364:


==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>
See references.
==References==
==References==
<references />
<references />
==Notes==
==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.
<nowiki>*</nowiki>''Citation of this Page'': Tizro P, Eno C, Kitahara S.“T-prolymphocytici leukemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 01/6/2026, <nowiki>https://ccga.io/index.php/HAEM5:T-prolymphocytic_leukaemia</nowiki>.
 
 
 
 
<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 [[Leadership|''Associate Editor'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.


Prior Author(s): N/A
[[Category:HAEM5]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:DISEASE]]
[[Category:Diseases T]]
[[Category:Diseases T]]
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