HAEM5:T-prolymphocytic leukaemia: Difference between revisions
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<span style="color:#0070C0">(''General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click nearby within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])''</span> | <span style="color:#0070C0">(''General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click nearby within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])''</span> | ||
==Primary Author(s)*== | ==Primary Author(s)*== | ||
Parastou Tizro, MD, Celeste Eno, PHD, Sumire Kitahara, MD | Parastou Tizro, MD, Celeste C. Eno, PHD, Sumire Kitahara, MD | ||
==WHO Classification of Disease== | ==WHO Classification of Disease== | ||
<span style="color:#0070C0">(Will be autogenerated; Book will include name of specific book and have a link to the online WHO site)</span> | <span style="color:#0070C0">(Will be autogenerated; Book will include name of specific book and have a link to the online WHO site)</span> | ||
| Line 59: | Line 59: | ||
Serum lactate dehydrogenase (LDH) (increased-may reflect disease burden) | Serum lactate dehydrogenase (LDH) (increased-may reflect disease burden) | ||
β2 microglobulin (B2M) (increased-may reflect disease burden) | |||
|} | |} | ||
==Sites of Involvement== | ==Sites of Involvement== | ||
Peripheral blood, bone marrow, spleen (mostly red pulp), liver, lymph node (mostly paracortical), and sometimes skin and serosa (primarily pleura). Extra lymphatic and extramedullary atypical manifestations including skin, muscles and intestines are particularly common in relapse. | Peripheral blood, bone marrow, spleen (mostly red pulp), liver, lymph node (mostly paracortical), and sometimes skin and serosa (primarily pleura). Extra lymphatic and extramedullary atypical manifestations including skin, muscles and intestines are particularly common in relapse.<ref name=":5" /> | ||
==Morphologic Features== | ==Morphologic Features== | ||
Blood smears in T-PLL typically reveal anemia, thrombocytopenia, and leukocytosis, with atypical lymphocytes in three morphological forms. The most common form (75% of cases) features medium-sized cells with a high nuclear-to-cytoplasmic ratio, moderately condensed chromatin, a single visible nucleolus, and slightly basophilic cytoplasm. In 20% of cases, the cells appear as a small cell variant with densely condensed chromatin and an inconspicuous nucleolus. About 5% of cases exhibit a cerebriform variant with irregular nuclei resembling those in mycosis fungoides. Regardless of the nuclear features, a common morphological characteristic is the presence of cytoplasmic protrusions or blebs.<ref>{{Cite journal|last=Gutierrez|first=Marc|last2=Bladek|first2=Patrick|last3=Goksu|first3=Busra|last4=Murga-Zamalloa|first4=Carlos|last5=Bixby|first5=Dale|last6=Wilcox|first6=Ryan|date=2023-07-28|title=T-Cell Prolymphocytic Leukemia: Diagnosis, Pathogenesis, and Treatment|url=https://pubmed.ncbi.nlm.nih.gov/37569479|journal=International Journal of Molecular Sciences|volume=24|issue=15|pages=12106|doi=10.3390/ijms241512106|issn=1422-0067|pmc=PMC10419310|pmid=37569479}}</ref>Bone marrow aspirates show clusters of these neoplastic cells, with a mixed pattern of involvement including diffuse and interstitial, in trephine core biopsy.<ref name=":6" /> | Blood smears in T-PLL typically reveal anemia, thrombocytopenia, and leukocytosis, with atypical lymphocytes in three morphological forms. The most common form (75% of cases) features medium-sized cells with a high nuclear-to-cytoplasmic ratio, moderately condensed chromatin, a single visible nucleolus, and slightly basophilic cytoplasm. In 20% of cases, the cells appear as a small cell variant with densely condensed chromatin and an inconspicuous nucleolus. About 5% of cases exhibit a cerebriform variant with irregular nuclei resembling those in mycosis fungoides. Regardless of the nuclear features, a common morphological characteristic is the presence of cytoplasmic protrusions or blebs.<ref>{{Cite journal|last=Gutierrez|first=Marc|last2=Bladek|first2=Patrick|last3=Goksu|first3=Busra|last4=Murga-Zamalloa|first4=Carlos|last5=Bixby|first5=Dale|last6=Wilcox|first6=Ryan|date=2023-07-28|title=T-Cell Prolymphocytic Leukemia: Diagnosis, Pathogenesis, and Treatment|url=https://pubmed.ncbi.nlm.nih.gov/37569479|journal=International Journal of Molecular Sciences|volume=24|issue=15|pages=12106|doi=10.3390/ijms241512106|issn=1422-0067|pmc=PMC10419310|pmid=37569479}}</ref>Bone marrow aspirates show clusters of these neoplastic cells, with a mixed pattern of involvement including diffuse and interstitial, in trephine core biopsy.<ref name=":6" /> | ||
==Immunophenotype== | ==Immunophenotype== | ||
T-cell prolymphocytes show strong staining with alpha-naphthyl acetate esterase and acid phosphatase, presenting a distinctive dot-like pattern, but cytochemistry is not commonly used for diagnosis.<ref>{{Cite journal|last=Yang|first=K.|last2=Bearman|first2=R. M.|last3=Pangalis|first3=G. A.|last4=Zelman|first4=R. J.|last5=Rappaport|first5=H.|date=1982-08|title=Acid phosphatase and alpha-naphthyl acetate esterase in neoplastic and non-neoplastic lymphocytes. A statistical analysis|url=https://pubmed.ncbi.nlm.nih.gov/6179423|journal=American Journal of Clinical Pathology|volume=78|issue=2|pages=141–149|doi=10.1093/ajcp/78.2.141|issn=0002-9173|pmid=6179423}}</ref> | T-cell prolymphocytes show strong staining with alpha-naphthyl acetate esterase and acid phosphatase, presenting a distinctive dot-like pattern, but cytochemistry is not commonly used for diagnosis.<ref>{{Cite journal|last=Yang|first=K.|last2=Bearman|first2=R. M.|last3=Pangalis|first3=G. A.|last4=Zelman|first4=R. J.|last5=Rappaport|first5=H.|date=1982-08|title=Acid phosphatase and alpha-naphthyl acetate esterase in neoplastic and non-neoplastic lymphocytes. A statistical analysis|url=https://pubmed.ncbi.nlm.nih.gov/6179423|journal=American Journal of Clinical Pathology|volume=78|issue=2|pages=141–149|doi=10.1093/ajcp/78.2.141|issn=0002-9173|pmid=6179423}}</ref> T-cell prolymphocytes exhibit a post-thymic T-cell phenotype. In 60% of cases, the cells are CD4+ and CD8-. In 25% of cases, they co-express both CD4 and CD8, while the remaining 15% are CD4- and CD8+.<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" | ||
|- | |- | ||
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|Positive (universal)||cyTCL1 (highest specificity), CD2, CD3 (may be weak), CD5, CD7 (strong), TCR-α/β, S100 (30% of cases) | |Positive (universal)||cyTCL1 (highest specificity), CD2, CD3 (may be weak), CD5, CD7 (strong), TCR-α/β, S100 (30% of cases) | ||
|- | |- | ||
|Positive (subset)||CD4 (in some cases CD4+/CD8+ or CD4-/CD8+), CD52 (therapeutic target), activation markers are variable (CD25, CD38, CD43, CD26, CD27) | |Positive (subset)||CD4 (in some cases CD4+/CD8+ or CD4-/CD8+), CD52 (usually expressed at high density, therapeutic target), activation markers are variable (CD25, CD38, CD43, CD26, CD27) | ||
|- | |- | ||
|Negative (universal)||TdT, CD1a, CD57, CD16, HTLV1 | |Negative (universal)||TdT, CD1a, CD57, CD16, HTLV1 | ||
| Line 81: | Line 81: | ||
|} | |} | ||
==Chromosomal Rearrangements (Gene Fusions)== | ==Chromosomal Rearrangements (Gene Fusions)== | ||
Rearrangements involving the TCL1 (T-cell leukemia/ | 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" /> | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
| Line 92: | Line 92: | ||
|inv(14)(q11.2q32.1) | |inv(14)(q11.2q32.1) | ||
t(14;14)(q11.2;q32.1) | t(14;14)(q11.2;q32.1) | ||
|TCL1A/B ,TRD|| ||inv(14) ~60% | |''TCL1A/B ,TRD''|| ||inv(14) ~60% | ||
t(14;14) ~25% | t(14;14) ~25% | ||
|Yes | |Yes | ||
|Yes | |Yes | ||
|Yes | |Yes | ||
|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" /> | |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" /> | ||
|- | |- | ||
|t(X;14)(q28;q11.2) | |t(X;14)(q28;q11.2) | ||
|MTCP1, TRD | |''MTCP1, TRD'' | ||
| | | | ||
|Low (5%) | |Low (5%) | ||
| | |Yes | ||
| | |No | ||
|Yes | |Yes | ||
|Major diagnostic criteria.<ref name=":6" /> | |Major diagnostic criteria.<ref name=":6" /> | ||
|} | |} | ||
==Individual Region Genomic Gain / Loss / LOH== | ==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. A list of clinically significant and/or recurrent CNAs and CN-LOH with potential or strong diagnostic, prognostic and treatment implications in T-PLL | 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" /> | ||
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" | {| class="wikitable sortable" | ||
|- | |- | ||
| Line 133: | Line 135: | ||
|No | |No | ||
|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">{{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> | ||
|- | |- | ||
|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> | ||
| | | | ||
|Yes | |Yes | ||
|Yes | |Yes | ||
|No | |No | ||
|Minor diagnostic criteria. <ref name=":6" /> | |Minor diagnostic criteria.<ref name=":6" /> | ||
|- | |- | ||
|6 | |6 | ||
|Abnormality | |Abnormality | ||
|6p | |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> | ||
| | | | ||
|No | |No | ||
| | |No | ||
| | |No | ||
| | | | ||
|- | |- | ||
| Line 167: | Line 169: | ||
|12p13 | |12p13 | ||
|Yes | |Yes | ||
| | |Yes | ||
| | |No | ||
|Minor diagnostic criteria.<ref name=":6" /> | |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> | ||
Minor diagnostic criteria.<ref name=":6" /> | |||
|- | |- | ||
|13 | |13 | ||
| Line 176: | Line 179: | ||
|13q14.3 | |13q14.3 | ||
|Yes | |Yes | ||
| | |No | ||
| | |No | ||
|Minor diagnostic criteria.<ref name=":6" /> | |Minor diagnostic criteria.<ref name=":6" /> | ||
|- | |- | ||
| Line 184: | Line 187: | ||
|17p, 17q | |17p, 17q | ||
|17p13 | |17p13 | ||
| | |No | ||
|Yes | |Yes | ||
|Yes (resistance to therapy) | |Yes (resistance to therapy) | ||
| | |The TP53 gene is deleted (at 17p13.1), with overexpression of p53, in some cases. <ref name=":7" /> | ||
|- | |- | ||
|22 | |22 | ||
| Line 197: | Line 200: | ||
(most common) | (most common) | ||
| | |Yes | ||
| | |No | ||
| | |No | ||
|Leading to the dysregulation of genes such as BCL11B, which is crucial in T-cell development and function.<ref name=":0" /> | |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" /> | Minor diagnostic criteria.<ref name=":6" /> | ||
|} | |} | ||
==Characteristic Chromosomal Patterns== | ==Diagnosis and Characteristic Chromosomal Patterns== | ||
[[File:Inv(14)(q11.2q32).png|thumb|Inv(14)(q11.2q32)]] | [[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:''' | |||
** 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 | |||
** Abnormalities of 14q32 or Xq28 or expression of TCL1A/B or MTC | |||
* '''Minor criteria:''' | |||
** Abnormalities involving chromosome 11 | |||
** Abnormalities in chromosome 8 | |||
** Abnormalities in chromosome 5, 12, 13, 22 or complex karyotype | |||
** Involvement of specific sites (spleen, effusions) | |||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
| Line 219: | Line 232: | ||
|Yes | |Yes | ||
|Yes | |Yes | ||
| | |he 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) | ||
|} | |} | ||
==Gene Mutations (SNV / INDEL)== | ==Gene Mutations (SNV / INDEL)== | ||
Although gene alterations are not yet | 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. AS 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 in diagnosing 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" /> | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
| Line 232: | Line 244: | ||
!Notes | !Notes | ||
|- | |- | ||
|ATM | |''ATM'' | ||
|TSG | |TSG | ||
|53% (COSMIC) | |53% (COSMIC) | ||
| Line 240: | Line 252: | ||
|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. | |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'' | ||
| Line 286: | Line 298: | ||
|None specified | |None specified | ||
|No | |No | ||
| | |No (see note) | ||
| | |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> | ||
|- | |- | ||
|''SAMHD1'' | |''SAMHD1'' | ||
|TSG | |TSG | ||
|~7-20%<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 | |~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 | ||
| Line 314: | Line 326: | ||
|2% (COSMIC) | |2% (COSMIC) | ||
|''ATM, JAK/STA''T pathway, Epigenetic modifiers | |''ATM, JAK/STA''T pathway, Epigenetic modifiers | ||
|None specified | |None specified-In a study of T-PLL case, TP53 mutations were predominantly found in patients lacking TCRA/D rearrangements.<ref name=":9" /> | ||
|No | |No | ||
|Yes | |Yes | ||
|Associated with resistance to therapy | |Associated with resistance to therapy | ||
|Mutations in TP53 are less frequent than deletions<ref | |Mutations in TP53 are less frequent than deletions.<ref name=":9" /> | ||
|}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 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== | ==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> | 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> | ||
==Genes and Main Pathways Involved== | ==Genes and Main Pathways Involved== | ||
The genetic landscape of T-PLL highlights the deregulation of DNA repair mechanisms and epigenetic modulators, alongside the frequent mutational activation of the IL2RG-JAK1-JAK3-STAT5B pathway in the pathogenesis of T-PLL.<ref name=":6" /> | |||
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