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| [[File:Inv(14)(q11.2q32).png|thumb|Inv(14)(q11.2q32)]]Diagnosis requires either all three major criteria or the first two major criteria along with one minor criterion:<ref name=":5" /> | | [[File:Inv(14)(q11.2q32).png|thumb|Inv(14)(q11.2q32)]]Diagnosis requires either all three major criteria or the first two major criteria along with one minor criterion:<ref name=":5" /> |
| | | |
− | * '''Major criteria:''' | + | *'''Major criteria:''' |
− | ** 5 x 10<sup>9</sup>/L cells of T PLL phenotype in peripheral blood or bone marrow | + | **5 x 10<sup>9</sup>/L cells of T PLL phenotype in peripheral blood or bone marrow |
− | ** T cell clonality by molecular or flow cytometry methods | + | **T cell clonality by molecular or flow cytometry methods |
− | ** Abnormalities of 14q32 or Xq28 or expression of TCL1A/B or MTC | + | **Abnormalities of 14q32 or Xq28 or expression of TCL1A/B or MTC |
− | * '''Minor criteria:''' | + | *'''Minor criteria:''' |
− | ** Abnormalities involving chromosome 11 | + | **Abnormalities involving chromosome 11 |
− | ** Abnormalities in chromosome 8 | + | **Abnormalities in chromosome 8 |
− | ** Abnormalities in chromosome 5, 12, 13, 22 or complex karyotype | + | **Abnormalities in chromosome 5, 12, 13, 22 or complex karyotype |
− | ** Involvement of specific sites (spleen, effusions) | + | **Involvement of specific sites (spleen, effusions) |
| | | |
| {| class="wikitable sortable" | | {| class="wikitable sortable" |
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| |Yes | | |Yes |
| |Yes (PARP inhibitors, NCT03263637) | | |Yes (PARP inhibitors, NCT03263637) |
− | |Deletions of or missense mutations at the ''ATM'' locus are found in up to 80% to 90% of T-PLL cases.<ref name=":8" /> ATM alterations can serve as a minor diagnostic criterion.<ref name=":6" /> | + | |Deletions of or missense mutations at the ''ATM'' locus are found in up to 80% to 90% of T-PLL cases.<ref name=":8" /> ATM alterations can serve as a minor diagnostic criterion.<ref name=":6" /> |
| |- | | |- |
| |''FBXW10'' | | |''FBXW10'' |
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| | | |
| (COSMIC) | | (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> | | |''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> | | |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 | | |Yes |
− | | | + | |Yes |
− | |The cumulative prevalence of these mutations in T-PLL is approximately 60%. (Dr jaffe book) | + | |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'' |
| |Oncogene, TSG | | |Oncogene, TSG |
| |16% (COSMIC) | | |16% (COSMIC) |
− | |JAK/STAT pathway<ref name=":1" /><ref name=":2" /> | + | |''JAK/STAT'' pathway<ref name=":1" /><ref name=":2" /> |
| |None specified | | |None specified |
| |No | | |No |
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| |TSG | | |TSG |
| |~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> | | |~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> |
− | | | + | |None specified |
| |None specified | | |None specified |
| |Yes | | |Yes |
− | | | + | |Yes |
− | | | + | |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" /> |
| |- | | |- |