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HAEM5:T-prolymphocytic leukaemia (view source)

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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" />

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* '''Major criteria:'''

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*'''Major criteria:'''

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** 5 x 10<sup>9</sup>/L cells of T PLL phenotype in peripheral blood or bone marrow

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**5 x 10<sup>9</sup>/L cells of T PLL phenotype in peripheral blood or bone marrow

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** T cell clonality by molecular or flow cytometry methods

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**T cell clonality by molecular or flow cytometry methods

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** Abnormalities of 14q32 or Xq28 or expression of TCL1A/B or MTC

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**Abnormalities of 14q32 or Xq28 or expression of TCL1A/B or MTC

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* '''Minor criteria:'''

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*'''Minor criteria:'''

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** Abnormalities involving chromosome 11

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**Abnormalities involving chromosome 11

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** Abnormalities in chromosome 8

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**Abnormalities in chromosome 8

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** Abnormalities in chromosome 5, 12, 13, 22 or complex karyotype

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**Abnormalities in chromosome 5, 12, 13, 22 or complex karyotype

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** Involvement of specific sites (spleen, effusions)

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**Involvement of specific sites (spleen, effusions)

{| class="wikitable sortable"

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|Yes

|Yes (PARP inhibitors, NCT03263637)

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|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" />

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|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" />

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|''FBXW10''

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(COSMIC)

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(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

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|

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|Yes

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|~~The cumulative prevalence of these mutations~~ in T-PLL ~~is approximately 60%~~. (~~Dr jaffe book~~)

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|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''

|Oncogene, TSG

|16% (COSMIC)

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|JAK/STAT pathway<ref name=":1" /><ref name=":2" />

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|''JAK/STAT'' pathway<ref name=":1" /><ref name=":2" />

|None specified

|No

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|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>

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|None specified

|Yes

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|Yes

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|No

|''SAMHD1'' mutations may indicate a defective DNA damage response and aggressive disease <ref name=":4" />

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Parastou.Tizro

35

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