Difference between revisions of "HAEM5:ALK-negative anaplastic large cell lymphoma"
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{{DISPLAYTITLE:ALK-negative anaplastic large cell lymphoma}} | {{DISPLAYTITLE:ALK-negative anaplastic large cell lymphoma}} | ||
| − | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]] | + | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]] |
{{Under Construction}} | {{Under Construction}} | ||
| − | <blockquote class="blockedit">{{Box-round|title= | + | <blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Anaplastic Large Cell Lymphoma, ALK-Negative]]. |
}}</blockquote> | }}</blockquote> | ||
| − | <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). 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 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)*== | ||
| Line 20: | Line 20: | ||
__TOC__ | __TOC__ | ||
| − | == | + | ==WHO Classification of Disease== |
| − | + | {| class="wikitable" | |
| − | + | !Structure | |
| − | + | !Disease | |
| − | + | |- | |
| − | + | |Book | |
| + | |Haematolymphoid Tumours (5th ed.) | ||
| + | |- | ||
| + | |Category | ||
| + | |T-cell and NK-cell lymphoid proliferations and lymphomas | ||
| + | |- | ||
| + | |Family | ||
| + | |Mature T-cell and NK-cell neoplasms | ||
| + | |- | ||
| + | |Type | ||
| + | |Anaplastic large cell lymphoma | ||
| + | |- | ||
| + | |Subtype(s) | ||
| + | |ALK-negative anaplastic large cell lymphoma | ||
| + | |} | ||
==Definition / Description of Disease== | ==Definition / Description of Disease== | ||
| Line 50: | Line 64: | ||
==Clinical Features== | ==Clinical Features== | ||
| − | Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span> | + | Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span> |
{| class="wikitable" | {| class="wikitable" | ||
|'''Signs and Symptoms''' | |'''Signs and Symptoms''' | ||
| Line 60: | Line 74: | ||
|- | |- | ||
|'''Laboratory Findings''' | |'''Laboratory Findings''' | ||
| − | | | + | |Not specific |
| − | |||
| − | |||
|} | |} | ||
| Line 159: | Line 171: | ||
|Yes | |Yes | ||
|No | |No | ||
| − | |<nowiki>*</nowiki> These rearrangements are considered mutually exclusive; however, a single case with both ''DUSP22'' and ''TP63'' rearrangement has been described<ref name=":11" />. Can also be seen in a fraction of other PTCL. | + | | |
| + | *<nowiki>*</nowiki> These rearrangements are considered mutually exclusive; however, a single case with both ''DUSP22'' and ''TP63'' rearrangement has been described<ref name=":11" />. Can also be seen in a fraction of other PTCL. | ||
| + | *5-year overall survival > 90% | ||
| + | *'''Therapeutic Implications''' | ||
| + | **Multi-agent chemotherapy (CHOEP or CHOP-based) as first-line, with or without radiotherapy of involved site | ||
| + | **High dose chemotherapy and autologous stem cell transplantation for remission | ||
| + | **DUSP22 subtype may not gain additional benefit from autologous stem cell transplantation in first remission | ||
| + | **Theoretical: | ||
| + | ***Ruxolitinib may be used to target JAK-STAT pathway<ref name=":13" /><ref name=":3" /> (not FDA-approved) | ||
| + | ***Bromodomain and extra-terminal proteins (BET) inhibitors may target ERBB4 pathway<ref name=":3" /><ref name=":14" /> | ||
|- | |- | ||
|*t(3;3)(q22;q26.2), inv(3)(q26q28) | |*t(3;3)(q22;q26.2), inv(3)(q26q28) | ||
|TP63/TBL1XR1<ref name=":12" /> | |TP63/TBL1XR1<ref name=":12" /> | ||
| − | |TP63/TBL1XR1 fusion protein | + | |TP63/TBL1XR1 fusion protein |
|8%<ref name=":0" /> | |8%<ref name=":0" /> | ||
|No | |No | ||
|Yes | |Yes | ||
|No | |No | ||
| − | |See t(6;7) notes | + | | |
| + | *<nowiki>*See t(6;7) notes</nowiki> | ||
| + | *5-year overall survival 17% | ||
|- | |- | ||
|t(10;19)(q24;p13) | |t(10;19)(q24;p13) | ||
| Line 178: | Line 201: | ||
|No | |No | ||
| | | | ||
| + | *5-year overall survival 42% for cases lacking all DUSP22, TP63 and ALK rearrangements<ref name=":0" /><ref name=":15" /> | ||
|- | |- | ||
|t(1;19)(p34;p13) | |t(1;19)(p34;p13) | ||
| Line 239: | Line 263: | ||
**When compared to ALK(+) ALCL, ALK(-) ALCL has a generally poorer prognosis, however: | **When compared to ALK(+) ALCL, ALK(-) ALCL has a generally poorer prognosis, however: | ||
***When stratified for age, prognosis between ALK(-) and ALK(+) ALCL appears similar <ref name=":8">{{Cite journal|last=Kj|first=Savage|last2=Nl|first2=Harris|last3=Jm|first3=Vose|last4=F|first4=Ullrich|last5=Es|first5=Jaffe|last6=Jm|first6=Connors|last7=L|first7=Rimsza|last8=Sa|first8=Pileri|last9=M|first9=Chhanabhai|date=2008|title=ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project|url=https://pubmed.ncbi.nlm.nih.gov/18385450/|language=en|pmid=18385450}}</ref><ref>{{Cite journal|last=D|first=Sibon|last2=M|first2=Fournier|last3=J|first3=Brière|last4=L|first4=Lamant|last5=C|first5=Haioun|last6=B|first6=Coiffier|last7=S|first7=Bologna|last8=P|first8=Morel|last9=J|first9=Gabarre|date=2012|title=Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials|url=https://pubmed.ncbi.nlm.nih.gov/23045585/|language=en|pmid=23045585}}</ref> | ***When stratified for age, prognosis between ALK(-) and ALK(+) ALCL appears similar <ref name=":8">{{Cite journal|last=Kj|first=Savage|last2=Nl|first2=Harris|last3=Jm|first3=Vose|last4=F|first4=Ullrich|last5=Es|first5=Jaffe|last6=Jm|first6=Connors|last7=L|first7=Rimsza|last8=Sa|first8=Pileri|last9=M|first9=Chhanabhai|date=2008|title=ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project|url=https://pubmed.ncbi.nlm.nih.gov/18385450/|language=en|pmid=18385450}}</ref><ref>{{Cite journal|last=D|first=Sibon|last2=M|first2=Fournier|last3=J|first3=Brière|last4=L|first4=Lamant|last5=C|first5=Haioun|last6=B|first6=Coiffier|last7=S|first7=Bologna|last8=P|first8=Morel|last9=J|first9=Gabarre|date=2012|title=Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials|url=https://pubmed.ncbi.nlm.nih.gov/23045585/|language=en|pmid=23045585}}</ref> | ||
| − | **5-year overall survival > 90% for DUSP22-rearranged ALK(-) ALCL, 17% for TP63-rearranged ALK(-) ALCL, and 42% for cases lacking all DUSP22, TP63 and ALK rearrangements<ref name=":0" /><ref>{{Cite journal|last=Mb|first=Pedersen|last2=Sj|first2=Hamilton-Dutoit|last3=K|first3=Bendix|last4=Rp|first4=Ketterling|last5=Pp|first5=Bedroske|last6=Im|first6=Luoma|last7=Ca|first7=Sattler|last8=Rl|first8=Boddicker|last9=Nn|first9=Bennani|date=2017|title=DUSP22 and TP63 rearrangements predict outcome of ALK-negative anaplastic large cell lymphoma: a Danish cohort study|url=https://pubmed.ncbi.nlm.nih.gov/28522440/|language=en|doi=10.1182/blood-2016-12-755496|pmc=PMC5533203|pmid=28522440}}</ref> | + | **5-year overall survival > 90% for DUSP22-rearranged ALK(-) ALCL, 17% for TP63-rearranged ALK(-) ALCL, and 42% for cases lacking all DUSP22, TP63 and ALK rearrangements<ref name=":0" /><ref name=":15">{{Cite journal|last=Mb|first=Pedersen|last2=Sj|first2=Hamilton-Dutoit|last3=K|first3=Bendix|last4=Rp|first4=Ketterling|last5=Pp|first5=Bedroske|last6=Im|first6=Luoma|last7=Ca|first7=Sattler|last8=Rl|first8=Boddicker|last9=Nn|first9=Bennani|date=2017|title=DUSP22 and TP63 rearrangements predict outcome of ALK-negative anaplastic large cell lymphoma: a Danish cohort study|url=https://pubmed.ncbi.nlm.nih.gov/28522440/|language=en|doi=10.1182/blood-2016-12-755496|pmc=PMC5533203|pmid=28522440}}</ref> |
**Patients with 6q21/PRDM1 and/or 17p loss showed an inferior outcome than patients with normal 6q21 and 17p; not clear if mainly due to [[TP53]] deletion due to study size<ref name=":5" /> | **Patients with 6q21/PRDM1 and/or 17p loss showed an inferior outcome than patients with normal 6q21 and 17p; not clear if mainly due to [[TP53]] deletion due to study size<ref name=":5" /> | ||
***Often concomitant loss and seen in almost a quarter of cases | ***Often concomitant loss and seen in almost a quarter of cases | ||
| Line 251: | Line 275: | ||
**DUSP22 subtype may not gain additional benefit from autologous stem cell transplantation in first remission | **DUSP22 subtype may not gain additional benefit from autologous stem cell transplantation in first remission | ||
**Theoretical: | **Theoretical: | ||
| − | ***Ruxolitinib may be used to target JAK-STAT pathway<ref>{{Cite journal|last=R|first=Roskoski|date=2016|title=Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases|url=https://pubmed.ncbi.nlm.nih.gov/27473820/|language=en|pmid=27473820}}</ref><ref name=":3">{{Cite journal|last=E|first=Mereu|last2=E|first2=Pellegrino|last3=I|first3=Scarfò|last4=G|first4=Inghirami|last5=R|first5=Piva|date=2017|title=The heterogeneous landscape of ALK negative ALCL|url=https://pubmed.ncbi.nlm.nih.gov/28061468/|language=en|doi=10.18632/oncotarget.14503|pmc=PMC5392347|pmid=28061468}}</ref> (not FDA-approved) | + | ***Ruxolitinib may be used to target JAK-STAT pathway<ref name=":13">{{Cite journal|last=R|first=Roskoski|date=2016|title=Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases|url=https://pubmed.ncbi.nlm.nih.gov/27473820/|language=en|pmid=27473820}}</ref><ref name=":3">{{Cite journal|last=E|first=Mereu|last2=E|first2=Pellegrino|last3=I|first3=Scarfò|last4=G|first4=Inghirami|last5=R|first5=Piva|date=2017|title=The heterogeneous landscape of ALK negative ALCL|url=https://pubmed.ncbi.nlm.nih.gov/28061468/|language=en|doi=10.18632/oncotarget.14503|pmc=PMC5392347|pmid=28061468}}</ref> (not FDA-approved) |
| − | ***Bromodomain and extra-terminal proteins (BET) inhibitors may target ERBB4 pathway<ref name=":3" /><ref>{{Cite journal|last=A|first=Chaidos|last2=V|first2=Caputo|last3=A|first3=Karadimitris|date=2015|title=Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence|url=https://pubmed.ncbi.nlm.nih.gov/26137204/|language=en|doi=10.1177/2040620715576662|pmc=PMC4480520|pmid=26137204}}</ref> | + | ***Bromodomain and extra-terminal proteins (BET) inhibitors may target ERBB4 pathway<ref name=":3" /><ref name=":14">{{Cite journal|last=A|first=Chaidos|last2=V|first2=Caputo|last3=A|first3=Karadimitris|date=2015|title=Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence|url=https://pubmed.ncbi.nlm.nih.gov/26137204/|language=en|doi=10.1177/2040620715576662|pmc=PMC4480520|pmid=26137204}}</ref> |
</blockquote> | </blockquote> | ||
==Individual Region Genomic Gain / Loss / LOH== | ==Individual Region Genomic Gain / Loss / LOH== | ||
| − | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span> | + | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.'') </span> |
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
| Line 267: | Line 291: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | | | + | |1q |
| − | + | |Gain | |
| − | + | | | |
| − | | | + | | |
| − | | | + | |No |
| − | + | |No | |
| − | + | |No | |
| − | | | + | | |
| − | + | *Prevalence 30% | |
| − | + | *Numerous genes affected | |
| − | | | + | |- |
| − | | | + | |6p |
| + | |Gain | ||
| + | |25.3 | ||
| + | | | ||
| + | |No | ||
| + | |No | ||
| + | |No | ||
| + | | | ||
| + | *Prevalence 30% | ||
| + | *Gene affected: ''DUSP22'' | ||
| + | |- | ||
| + | |8q | ||
| + | |Gain | ||
| + | |24.22 | ||
| + | | | ||
| + | |No | ||
| + | |No | ||
| + | |No | ||
| + | | | ||
| + | *Prevalence 16-23% | ||
| + | *Genes affected: NDRG1, ''PHF20L1, SLA, ST3GAL1, TG, WISP1'' | ||
| + | |- | ||
| + | |1p | ||
| + | |Loss | ||
| + | |13.3-p12 | ||
| + | 36.33-36.32 | ||
| + | | | ||
| + | |No | ||
| + | |No | ||
| + | |No | ||
| + | | | ||
| + | *Prevalence 19-26% | ||
| + | |- | ||
| + | |'''6q''' | ||
| + | |'''Loss > CN-LOH''' | ||
| + | |21 | ||
| + | | | ||
| + | |No | ||
| + | |No | ||
| + | |No | ||
| + | | | ||
| + | *Prevalence 35% | ||
| + | *Genes affected: '''''PRDM1''', ATG5'' | ||
| + | |- | ||
| + | |10p | ||
| + | |Loss | ||
| + | |11.23-p11.22 | ||
| + | | | ||
| + | |No | ||
| + | |No | ||
| + | |No | ||
| + | | | ||
| + | *Prevalence 23% | ||
| + | |- | ||
| + | |13q | ||
| + | |Loss | ||
| + | |32.3-q33.3 | ||
| + | | | ||
| + | |No | ||
| + | |No | ||
|No | |No | ||
| − | | | + | | |
| − | + | *Prevalence 23% | |
| − | + | *Genes affected: ''CDC16, CUL4A,FOXO1A, BRCA2, LHFP, LCP1'' | |
|- | |- | ||
| − | | | + | |16q |
| − | + | |Loss | |
| − | + | |23.2 | |
| − | | | + | | |
| − | | | ||
| − | |||
| − | |||
| − | | | ||
| − | |||
| − | |||
|No | |No | ||
|No | |No | ||
|No | |No | ||
| − | | | + | | |
| − | + | *Prevalence 29% | |
| − | + | *Genes affected: ''MAF, WWOX'' | |
| + | |- | ||
| + | |17p | ||
| + | |Loss | ||
| + | |'''13.3-p12''' | ||
| + | | | ||
| + | |No | ||
| + | |Yes?** | ||
| + | |No | ||
| + | | | ||
| + | *Prevalence: 42% | ||
| + | *Gene affected: ''TP53'' | ||
|} | |} | ||
| Line 372: | Line 460: | ||
==Characteristic Chromosomal Patterns== | ==Characteristic Chromosomal Patterns== | ||
| − | Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: 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'')</span> | + | Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: 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. Do not delete table.'')</span> |
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
| Line 382: | Line 470: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | | | + | |N/A |
| − | + | |N/A | |
| − | + | |N/A | |
| − | | | + | |N/A |
| − | | | + | |N/A |
| − | | | ||
| − | | | ||
| − | |||
| − | |||
|} | |} | ||
| Line 402: | Line 486: | ||
==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 and common as well either disease defining and/or clinically significant. Can include references 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 | + | 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 and common as well as either disease defining and/or clinically significant. Can include references 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. Do not delete table.'') </span> |
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
| Line 412: | Line 496: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | | | + | |''TP53'' |
| + | |TSG | ||
| + | |23%<ref name=":6" /> | ||
| + | |No | ||
| + | |N/A | ||
| + | |No | ||
| + | |Yes | ||
| + | |No | ||
| + | |<br /> | ||
| + | |- | ||
| + | |''STAT3'' | ||
| + | |Oncogene | ||
| + | |26%<ref name=":6" /> | ||
| + | |No | ||
| + | |N/A | ||
| + | |No | ||
| + | |Yes | ||
| + | |No | ||
| + | | | ||
| + | * Not seen in PTCL-NOS<ref name=":2" /> or ALK+ ALCL<ref name=":2" /><ref name=":6" /> | ||
| − | + | *Ruxolitinib may be used to target JAK-STAT pathway (not FDA-approved)<ref name=":13" /> | |
| − | + | |- | |
| − | + | |''JAK1'' | |
| − | + | |Oncogene | |
| − | + | |26%<ref name=":6" /> | |
| − | | | + | |No |
| − | | | + | |N/A |
| − | + | |No | |
| − | + | |Yes | |
| − | | | + | |No |
| − | | | + | | |
| + | * Not seen in PTCL-NOS<ref name=":2" /> or ALK+ ALCL<ref name=":2" /><ref name=":6" /> | ||
| + | |- | ||
| + | |PRDM1/BLIMP1<ref name=":5" /> | ||
| + | |TSG | ||
| + | |6% | ||
| + | |No | ||
| + | |N/A | ||
| + | |No | ||
| + | |No | ||
| + | |No | ||
| | | | ||
| + | |- | ||
| + | |[[NOTCH1]]<ref name=":16" /> | ||
| + | |Oncogene | ||
| + | |15% | ||
| + | |No | ||
| + | |No | ||
| + | |No | ||
| + | |No | ||
| + | |No | ||
| | | | ||
| + | |- | ||
| + | |KMT2D<ref name=":6" /> | ||
| + | |TSG | ||
| + | |20% | ||
| + | |No | ||
| + | |No | ||
| + | |No | ||
| + | |No | ||
| + | |No | ||
| | | | ||
| − | |||
| − | |||
|} | |} | ||
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. | ||
| Line 456: | Line 585: | ||
| | | | ||
|- | |- | ||
| − | |[[NOTCH1]]<ref>{{Cite journal|last=Larose|first=Hugo|last2=Prokoph|first2=Nina|last3=Matthews|first3=Jamie D.|last4=Schlederer|first4=Michaela|last5=Högler|first5=Sandra|last6=Alsulami|first6=Ali F.|last7=Ducray|first7=Stephen P.|last8=Nuglozeh|first8=Edem|last9=Fazaludeen|first9=Feroze M. S.|date=2020-04-23|title=Whole Exome Sequencing reveals NOTCH1 mutations in anaplastic large cell lymphoma and points to Notch both as a key pathway and a potential therapeutic target|url=https://haematologica.org/article/view/9725|journal=Haematologica|language=en|doi=10.3324/haematol.2019.238766|issn=1592-8721}}</ref> | + | |[[NOTCH1]]<ref name=":16">{{Cite journal|last=Larose|first=Hugo|last2=Prokoph|first2=Nina|last3=Matthews|first3=Jamie D.|last4=Schlederer|first4=Michaela|last5=Högler|first5=Sandra|last6=Alsulami|first6=Ali F.|last7=Ducray|first7=Stephen P.|last8=Nuglozeh|first8=Edem|last9=Fazaludeen|first9=Feroze M. S.|date=2020-04-23|title=Whole Exome Sequencing reveals NOTCH1 mutations in anaplastic large cell lymphoma and points to Notch both as a key pathway and a potential therapeutic target|url=https://haematologica.org/article/view/9725|journal=Haematologica|language=en|doi=10.3324/haematol.2019.238766|issn=1592-8721}}</ref> |
|Activating | |Activating | ||
|15% | |15% | ||
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==Genes and Main Pathways Involved== | ==Genes and Main Pathways Involved== | ||
| − | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span> | + | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span> |
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome | !Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome | ||
|- | |- | ||
| − | | | + | |''STAT3''<ref name=":2" /> |
| − | | | + | |JAK-STAT pathway |
| − | | | + | |Increased cell growth and proliferation |
|- | |- | ||
| − | | | + | |''NFkB2-ROS1'' fusion<ref name=":2" /> |
| − | | | + | |JAK-STAT pathway |
| − | | | + | |Increased cell growth and proliferation |
|- | |- | ||
| − | | | + | |''NFkB2-TYK2'' fusion<ref name=":2" /> |
| − | | | + | |JAK-STAT pathway |
| − | | | + | |Increased cell growth and proliferation |
|} | |} | ||
Latest revision as of 17:38, 6 September 2024
Haematolymphoid Tumours (WHO Classification, 5th ed.)
 | This page is under construction |
editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition ClassificationThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Anaplastic Large Cell Lymphoma, ALK-Negative.
(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), 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 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 Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)
Primary Author(s)*
Miguel Gonzalez Mancera, MD
Sumire Kitahara, MD
Cedars-Sinai, Los Angeles, CA
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Haematolymphoid Tumours (5th ed.) |
| Category | T-cell and NK-cell lymphoid proliferations and lymphomas |
| Family | Mature T-cell and NK-cell neoplasms |
| Type | Anaplastic large cell lymphoma |
| Subtype(s) | ALK-negative anaplastic large cell lymphoma |
Definition / Description of Disease
- Anaplastic large cell lymphomas (ALCL), ALK-negative, is a CD30+ T-cell lymphoma that is morphologically and immunophenotypically indistinguishable (but lacks ALK protein expression) from ALK(+) ALCL[1][2]
- Three major molecular subtypes of ALK (-) ALCL[1][2]:
- DUSP22-rearranged subtype (30%)
- TP63-rearranged subtype (8%)
- Triple-negative subtype (DUSP22 negative, TP63 negative, ALK negative)
- Emerging subtypes:
- ERBB4 expression (~25%): mutually exclusive with other rearrangements (TP63, DUSP22, ROS or TYK translocations)[3]
Synonyms / Terminology
- N/A
Epidemiology / Prevalence
- More common in adults than children (peak incidence 6th decade of life)[4]
- Less than 3% of all Non-Hodgkin's lymphoma[4]
- M:F 1.5:1[4]
Clinical Features
Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)
| Signs and Symptoms | B-symptoms (weight loss, fever, night sweats)[4]
Peripheral and/or Lymphadenopathy[4] Most patients present with advanced stage disease[4] |
| Laboratory Findings | Not specific |
editv4:Clinical FeaturesThe content below was from the old template. Please incorporate above.
Sites of Involvement
- Nodal (predominantly abdominal lymphadenopathy) in a sinusoidal pattern
- Extranodal (skin, soft tissue, gastrointestinal, bone) in about 20% of cases
- If involving the skin or GI tract, cases must be distinguished from primary cutaneous ALCL or CD30+ enteropathy-associated/other intestinal T-cell lymphomas, respectively
Morphologic Features
- Tissue effacement by cohesive sheets of large, pleomorphic neoplastic cells, with or without prominent nucleoli, with varying proportions of hallmark cells
- "Hallmark cells"
- Lymphoma cells characterized by eccentric, horseshoe-shaped or kidney-shaped nuclei, often with eosinophilic cytoplasm accentuated near the nucleus
- Usually large in size, but may also be smaller
- Less common that in classic variant of ALK (+) ALCL
- DUSP22-rearranged subtype tends to lack large pleomorphic cells and show smaller, monomorphic cells with central nuclear pseudoinclusions (doughnut cells)
- Intrasinusoidal growth pattern seen in cases with preserved nodal architecture
Immunophenotype
Immunohistochemical patterns vary by subtype[4][5][6]
DUSP22-rearranged subtype
| Finding | Marker |
|---|---|
| Positive (universal) | CD30*, CD43 (almost universally) |
| Negative (universal) | ALK, TP63, EBER, LMP-1 |
| Positive (frequent) | CD2, CD3, CD4+ cases more common than CD8, CD5, Clusterin |
| Negative (frequent) | TIAI, granzyme B, perforin, EMA, PAX5 |
*Strong and diffuse CD30 staining; should be equal intensity in all cells
TP63-rearranged subtype
| Finding | Marker |
|---|---|
| Positive (universal) | CD30*, CD43 (almost universally), P63, CD4+ cases more common than CD8 |
| Negative (universal) | ALK, EBER, LMP-1 |
| Positive (frequent) | CD2, CD3, CD4, CD5, TIA1, granzyme B, perforin, clusterin |
| Negative (very frequent) | EMA |
Triple-negative subtype
| Finding | Marker |
|---|---|
| Positive (universal) | CD30*, CD43 (almost universally), CD2, CD3, CD4+ cases more common than CD8, CD5, TIA1, granzyme B, perforin, EMA |
| Negative (universal) | ALK, P63, EBER, LMP-1 |
| Positive (common) | EMA, clusterin |
| Negative (frequent) | PAX5, CD20, CD79a, CD15 |
Chromosomal Rearrangements (Gene Fusions)
Put your text here and fill in the table
| 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 |
|---|---|---|---|---|---|---|---|
| *t(6;7)(p25.3;q32.3) | DUSP22/FRA7H[7] | DUSP22/FRA7H fusion protein | 30%[6] | No | Yes | No |
|
| *t(3;3)(q22;q26.2), inv(3)(q26q28) | TP63/TBL1XR1[12] | TP63/TBL1XR1 fusion protein | 8%[6] | No | Yes | No |
|
| t(10;19)(q24;p13) | NFKB2/TYK2 | NFKB2/TYK2 fusion protein | rare[13] | No | No | No | |
| t(1;19)(p34;p13) | PABPC4/TYK2 | PABPC4/TYK2 fusion protein | rare[13] | No | No | No | |
| t(6;10)(q22;q24) | NFKB2/ROS1 | NFKB2/ROS1 fusion protein | rare[13] | No | No | No |
editv4:Chromosomal Rearrangements (Gene Fusions)The content below was from the old template. Please incorporate above.
Chromosomal Rearrangement[15][16] Genes in Fusion (5’ or 3’ Segments) Prevalence *t(6;7)(p25.3;q32.3) DUSP22/FRA7H[7] 30%[6] *t(3;3)(q22;q26.2), inv(3)(q26q28) TP63/TBL1XR1[12] 8%[6] t(10;19)(q24;p13) NFKB2/TYK2 rare[13] t(1;19)(p34;p13) PABPC4/TYK2 rare[13] t(6;10)(q22;q24) NFKB2/ROS1 rare[13] * These rearrangements are considered mutually exclusive; however, a single case with both DUSP22 and TP63 rearrangement has been described[8]. Can also be seen in a fraction of other PTCL.
editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).Please incorporate this section into the relevant tables found in:
- Chromosomal Rearrangements (Gene Fusions)
- Individual Region Genomic Gain/Loss/LOH
- Characteristic Chromosomal Patterns
- Gene Mutations (SNV/INDEL)
- Diagnosis
- Prognosis
- When compared to ALK(+) ALCL, ALK(-) ALCL has a generally poorer prognosis, however:
- 5-year overall survival > 90% for DUSP22-rearranged ALK(-) ALCL, 17% for TP63-rearranged ALK(-) ALCL, and 42% for cases lacking all DUSP22, TP63 and ALK rearrangements[6][14]
- Patients with 6q21/PRDM1 and/or 17p loss showed an inferior outcome than patients with normal 6q21 and 17p; not clear if mainly due to TP53 deletion due to study size[19]
- Often concomitant loss and seen in almost a quarter of cases
- Mutations with significantly shorter OS compared to wild-type[20]
- STAT3, TP53
- Prognostic significance of ERB4 and COL29A1 co-expressing subtypes unclear [3]
- Therapeutic Implications
- Multi-agent chemotherapy (CHOEP or CHOP-based) as first-line, with or without radiotherapy of involved site
- High dose chemotherapy and autologous stem cell transplantation for remission
- DUSP22 subtype may not gain additional benefit from autologous stem cell transplantation in first remission
- Theoretical:
Individual Region Genomic Gain / Loss / LOH
Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.)
| 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 |
|---|---|---|---|---|---|---|---|
| 1q | Gain | No | No | No |
| ||
| 6p | Gain | 25.3 | No | No | No |
| |
| 8q | Gain | 24.22 | No | No | No |
| |
| 1p | Loss | 13.3-p12
36.33-36.32 |
No | No | No |
| |
| 6q | Loss > CN-LOH | 21 | No | No | No |
| |
| 10p | Loss | 11.23-p11.22 | No | No | No |
| |
| 13q | Loss | 32.3-q33.3 | No | No | No |
| |
| 16q | Loss | 23.2 | No | No | No |
| |
| 17p | Loss | 13.3-p12 | No | Yes?** | No |
|
editv4:Genomic Gain/Loss/LOHThe content below was from the old template. Please incorporate above.The pattern of genomic copy number changes and loss of heterozygosity have been described[19][21][22]:
- In general, recurrent lesions are more common in ALK(-) than ALK(+) disease
- 6q21 losses associated with 17p deletions seen in ~25% of cases of ALK(-) ALCL[19]
- None are diagnostically helpful for the distinction between ALK(-) ALCL from other entities
Chromosome Number Gain/Loss/Amp/LOH Region Genes Prevalence 1q Gain numerous 30% 6p Gain 25.3 DUSP22 30% 8q Gain 24.22 NDRG1, PHF20L1, SLA, ST3GAL1, TG, WISP1 16-23% 1p Loss 13.3-p12 36.33-36.32
26% 19%
6q Loss > CN-LOH; See also below for somatic mutations
21 PRDM1, ATG5 35% 10p Loss 11.23-p11.22 23% 13q Loss 32.3-q33.3 CDC16, CUL4A,FOXO1A, BRCA2, LHFP, LCP1 23% 16q Loss 23.2 MAF, WWOX 29% 17p Loss 13.3-p12 TP53 42%
Characteristic Chromosomal Patterns
Put your text here (EXAMPLE PATTERNS: 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. Do not delete table.)
| Chromosomal Pattern | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|
| N/A | N/A | N/A | N/A | N/A |
editv4:Characteristic Chromosomal Aberrations / PatternsThe content below was from the old template. Please incorporate above.
- Gene expression profiling and comparative genomic hybridization studies have shown that ALK(+) and ALK(-) ALCL share restricted genomic signatures and/or preferential genomic aberrations[23][24][25]
- Several genes are similarly expressed in ALK(+) and ALK(-) samples, suggesting a common ALCL signature, that permit differential diagnosis of ALCL from PTCL-NOS[26]
- See other sections.
Gene Mutations (SNV / INDEL)
Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references 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. Do not delete table.)
| 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 |
|---|---|---|---|---|---|---|---|---|
| TP53 | TSG | 23%[20] | No | N/A | No | Yes | No | |
| STAT3 | Oncogene | 26%[20] | No | N/A | No | Yes | No |
|
| JAK1 | Oncogene | 26%[20] | No | N/A | No | Yes | No | |
| PRDM1/BLIMP1[19] | TSG | 6% | No | N/A | No | No | No | |
| NOTCH1[27] | Oncogene | 15% | No | No | No | No | No | |
| KMT2D[20] | TSG | 20% | No | No | No | No | No |
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.
editv4:Gene Mutations (SNV/INDEL)The content below was from the old template. Please incorporate above.
Gene Presumed mechanism Frequency Notes STAT3*[13][20] Activating 10-26% Not seen in PTCL-NOS[13] or ALK+ ALCL[13][20] JAK1*[13][20] Activating 15-26% Not seen in PTCL-NOS[13] or ALK+ ALCL[13][20] PRDM1/BLIMP1[19] Tumor suppressor 6% (2/31) NOTCH1[27] Activating 15% TP53[20] Tumor suppressor 23% KMT2D[20] Tumor suppressor 20% *Double mutated for JAK1+STAT3 in 7-11%[13][20]
Other mutations
Epigenomic Alterations
- See above mutations in epigenetic modifier genes
Genes and Main Pathways Involved
Put your text here and fill in the table (Instructions: Can include references in the table. Do not delete table.)
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| STAT3[13] | JAK-STAT pathway | Increased cell growth and proliferation |
| NFkB2-ROS1 fusion[13] | JAK-STAT pathway | Increased cell growth and proliferation |
| NFkB2-TYK2 fusion[13] | JAK-STAT pathway | Increased cell growth and proliferation |
editv4:Genes and Main Pathways InvolvedThe content below was from the old template. Please incorporate above.
- JAK-STAT[13]
- STAT3 mutants are constitutively phosphorylated
- JAK1 mutants lead to the constitutive phosphorylation of STAT and synergize with STAT3 mutants
- When JAK/STAT3 mutations absent, NFkB2-ROS1 and NFkB2-TYK2 fusions may constitutively activate STAT pathway
Genetic Diagnostic Testing Methods
- Morphologic and immunophenotypic characterization
- Strong CD30 staining of equal intensity help distinguish from PTCL, NOS, classic Hodgkin lymphoma, diffuse large B-cell lymphoma, and monomorphic epitheliotropic intestinal T-cell lymphoma
- Exclusion of ALK(+) ALCL cases by immunostain for ALK
- P63 immunostain to identify TP63 rearranged. Immunophenotyping is not sensitive and is thus used as screening before FISH analysis. A ≥ 30% threshold yields 100% sensitivity[28]
- Presence of STAT3 and/or JAK1 mutations seem to favor ALK(-) ALCL over PTCL-NOS[13]
- FISH studies necessary to subtype:
- DUSP22 (IRF4/DUSP22) break-apart probe
- TP63 rearrangement
- ERBB4(+) cases may be identified using digital droplet PCR or immunostaining for MMP9 (a protein highly correlated with ERBB4 expression)
- Not routinely performed
Familial Forms
- Not described
Additional Information
- None
Links
- See references.
References
(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)
- ↑ 1.0 1.1 Ad, Attygalle; et al. (2014). "Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward - report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology". doi:10.1111/his.12251. PMC 6364972. PMID 24128129.CS1 maint: PMC format (link)
- ↑ 2.0 2.1 2.2 Sh, Swerdlow; et al. (2016). "The 2016 revision of the World Health Organization classification of lymphoid neoplasms". doi:10.1182/blood-2016-01-643569. PMC 4874220. PMID 26980727.CS1 maint: PMC format (link)
- ↑ 3.0 3.1 I, Scarfò; et al. (2016). "Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts". PMID 26463425.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 G, Hapgood; et al. (2015). "The biology and management of systemic anaplastic large cell lymphoma". PMID 25869285.
- ↑ M, Herling; et al. (2004). "Absence of Epstein-Barr virus in anaplastic large cell lymphoma: a study of 64 cases classified according to World Health Organization criteria". PMID 15116326.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 Er, Parrilla Castellar; et al. (2014). "ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes". doi:10.1182/blood-2014-04-571091. PMC 4148769. PMID 24894770.CS1 maint: PMC format (link)
- ↑ 7.0 7.1 Feldman, Andrew L.; et al. (2011-01-20). "Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing". Blood. 117 (3): 915–919. doi:10.1182/blood-2010-08-303305. ISSN 1528-0020. PMC 3035081. PMID 21030553.
- ↑ 8.0 8.1 K, Karube; et al. (2020). ""Double-hit" of DUSP22 and TP63 rearrangements in anaplastic large cell lymphoma, ALK-negative". PMID 32106310 Check
|pmid=value (help). - ↑ 9.0 9.1 9.2 R, Roskoski (2016). "Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases". PMID 27473820.
- ↑ 10.0 10.1 10.2 10.3 E, Mereu; et al. (2017). "The heterogeneous landscape of ALK negative ALCL". doi:10.18632/oncotarget.14503. PMC 5392347. PMID 28061468.CS1 maint: PMC format (link)
- ↑ 11.0 11.1 A, Chaidos; et al. (2015). "Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence". doi:10.1177/2040620715576662. PMC 4480520. PMID 26137204.CS1 maint: PMC format (link)
- ↑ 12.0 12.1 Vasmatzis, George; et al. (2012-09-13). "Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas". Blood. 120 (11): 2280–2289. doi:10.1182/blood-2012-03-419937. ISSN 1528-0020. PMC 5070713. PMID 22855598.
- ↑ 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 13.11 13.12 13.13 13.14 13.15 13.16 13.17 13.18 13.19 13.20 13.21 13.22 13.23 R, Crescenzo; et al. (2015). "Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma". doi:10.1016/j.ccell.2015.03.006. PMC 5898430. PMID 25873174.CS1 maint: PMC format (link)
- ↑ 14.0 14.1 Mb, Pedersen; et al. (2017). "DUSP22 and TP63 rearrangements predict outcome of ALK-negative anaplastic large cell lymphoma: a Danish cohort study". doi:10.1182/blood-2016-12-755496. PMC 5533203. PMID 28522440.CS1 maint: PMC format (link)
- ↑ Pileri, Stefano (2011-05-01). "Faculty Opinions recommendation of Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing".
- ↑ Da, Wada; et al. (2011). "Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies". doi:10.1038/modpathol.2010.225. PMC 3122134. PMID 21169992.CS1 maint: PMC format (link)
- ↑ 17.0 17.1 Kj, Savage; et al. (2008). "ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project". PMID 18385450.
- ↑ D, Sibon; et al. (2012). "Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials". PMID 23045585.
- ↑ 19.0 19.1 19.2 19.3 19.4 M, Boi; et al. (2013). "PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma". PMID 24004669.
- ↑ 20.00 20.01 20.02 20.03 20.04 20.05 20.06 20.07 20.08 20.09 20.10 20.11 20.12 20.13 20.14 20.15 Lobello, Cosimo; et al. (2020-11-27). "STAT3 and TP53 mutations associate with poor prognosis in anaplastic large cell lymphoma". Leukemia: 1–6. doi:10.1038/s41375-020-01093-1. ISSN 1476-5551.
- ↑ G, Vasmatzis; et al. (2012). "Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas". doi:10.1182/blood-2012-03-419937. PMC 5070713. PMID 22855598.CS1 maint: PMC format (link)
- ↑ Y, Zeng; et al. (2016). "Genetics of anaplastic large cell lymphoma". doi:10.3109/10428194.2015.1064530. PMC 4732699. PMID 26104084.CS1 maint: PMC format (link)
- ↑ Thompson, Mary Ann; et al. (2005-05). "Differential gene expression in anaplastic lymphoma kinase-positive and anaplastic lymphoma kinase-negative anaplastic large cell lymphomas". Human Pathology. 36 (5): 494–504. doi:10.1016/j.humpath.2005.03.004. ISSN 0046-8177. PMID 15948116. Check date values in:
|date=(help) - ↑ Piccaluga, Pier Paolo; et al. (2007-03). "Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets". The Journal of Clinical Investigation. 117 (3): 823–834. doi:10.1172/JCI26833. ISSN 0021-9738. PMC 1794115. PMID 17304354. Check date values in:
|date=(help) - ↑ Salaverria, Itziar; et al. (2008-03). "Genomic profiling reveals different genetic aberrations in systemic ALK-positive and ALK-negative anaplastic large cell lymphomas". British Journal of Haematology. 140 (5): 516–526. doi:10.1111/j.1365-2141.2007.06924.x. ISSN 1365-2141. PMID 18275429. Check date values in:
|date=(help) - ↑ Piva, Roberto; et al. (2010-03-20). "Gene expression profiling uncovers molecular classifiers for the recognition of anaplastic large-cell lymphoma within peripheral T-cell neoplasms". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 28 (9): 1583–1590. doi:10.1200/JCO.2008.20.9759. ISSN 1527-7755. PMID 20159827.
- ↑ 27.0 27.1 Larose, Hugo; et al. (2020-04-23). "Whole Exome Sequencing reveals NOTCH1 mutations in anaplastic large cell lymphoma and points to Notch both as a key pathway and a potential therapeutic target". Haematologica. doi:10.3324/haematol.2019.238766. ISSN 1592-8721.
- ↑ X, Wang; et al. (2017). "Expression of p63 protein in anaplastic large cell lymphoma: implications for genetic subtyping". doi:10.1016/j.humpath.2017.01.003. PMC 5518937. PMID 28153507.CS1 maint: PMC format (link)
Notes
*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. *Citation of this Page: “ALK-negative anaplastic large cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:ALK-negative_anaplastic_large_cell_lymphoma.