HAEM5:ALK-negative anaplastic large cell lymphoma: Difference between revisions

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*B symptoms of weight loss, fevers, chills<ref name=":1" />

*Most patients present with advanced stage disease<ref name=":1" />

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==Sites of Involvement==

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<nowiki>*</nowiki> These rearrangements are considered mutually exclusive; however, a single case with both ''DUSP22'' and ''TP63'' rearrangement has been described<ref name=":11">{{Cite journal|last=K|first=Karube|last2=Al|first2=Feldman|date=2020|title="Double-hit" of DUSP22 and TP63 rearrangements in anaplastic large cell lymphoma, ALK-negative|url=https://pubmed.ncbi.nlm.nih.gov/32106310/|language=en|pmid=32106310}}</ref>. Can also be seen in a fraction of other PTCL.

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* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

*'''Diagnosis'''  

***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>

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==Individual Region Genomic Gain / Loss / LOH==

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The pattern of genomic copy number changes and loss of heterozygosity have been described<ref name=":5">{{Cite journal|last=M|first=Boi|last2=A|first2=Rinaldi|last3=I|first3=Kwee|last4=P|first4=Bonetti|last5=M|first5=Todaro|last6=F|first6=Tabbò|last7=R|first7=Piva|last8=Pm|first8=Rancoita|last9=A|first9=Matolcsy|date=2013|title=PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/24004669/|language=en|pmid=24004669}}</ref><ref>{{Cite journal|last=G|first=Vasmatzis|last2=Sh|first2=Johnson|last3=Ra|first3=Knudson|last4=Rp|first4=Ketterling|last5=E|first5=Braggio|last6=R|first6=Fonseca|last7=Ds|first7=Viswanatha|last8=Me|first8=Law|last9=Ns|first9=Kip|date=2012|title=Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/22855598/|language=en|doi=10.1182/blood-2012-03-419937|pmc=PMC5070713|pmid=22855598}}</ref><ref>{{Cite journal|last=Y|first=Zeng|last2=Al|first2=Feldman|date=2016|title=Genetics of anaplastic large cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26104084/|language=en|doi=10.3109/10428194.2015.1064530|pmc=PMC4732699|pmid=26104084}}</ref>:

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==Characteristic Chromosomal Patterns==

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*Gene expression profiling and comparative genomic hybridization studies have shown that ALK(+) and ALK(-) ALCL share restricted genomic signatures and/or preferential genomic aberrations<ref>{{Cite journal|last=Thompson|first=Mary Ann|last2=Stumph|first2=Jennifer|last3=Henrickson|first3=Sarah E.|last4=Rosenwald|first4=Andreas|last5=Wang|first5=Qifu|last6=Olson|first6=Sandy|last7=Brandt|first7=Stephen J.|last8=Roberts|first8=Jeremy|last9=Zhang|first9=Xueqiong|date=2005-05|title=Differential gene expression in anaplastic lymphoma kinase-positive and anaplastic lymphoma kinase-negative anaplastic large cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/15948116|journal=Human Pathology|volume=36|issue=5|pages=494–504|doi=10.1016/j.humpath.2005.03.004|issn=0046-8177|pmid=15948116}}</ref><ref>{{Cite journal|last=Piccaluga|first=Pier Paolo|last2=Agostinelli|first2=Claudio|last3=Califano|first3=Andrea|last4=Rossi|first4=Maura|last5=Basso|first5=Katia|last6=Zupo|first6=Simonetta|last7=Went|first7=Philip|last8=Klein|first8=Ulf|last9=Zinzani|first9=Pier Luigi|date=2007-03|title=Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets|url=https://pubmed.ncbi.nlm.nih.gov/17304354|journal=The Journal of Clinical Investigation|volume=117|issue=3|pages=823–834|doi=10.1172/JCI26833|issn=0021-9738|pmc=1794115|pmid=17304354}}</ref><ref>{{Cite journal|last=Salaverria|first=Itziar|last2=Beà|first2=Silvia|last3=Lopez-Guillermo|first3=Armando|last4=Lespinet|first4=Virginia|last5=Pinyol|first5=Magda|last6=Burkhardt|first6=Birgit|last7=Lamant|first7=Laurence|last8=Zettl|first8=Andreas|last9=Horsman|first9=Doug|date=2008-03|title=Genomic profiling reveals different genetic aberrations in systemic ALK-positive and ALK-negative anaplastic large cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/18275429|journal=British Journal of Haematology|volume=140|issue=5|pages=516–526|doi=10.1111/j.1365-2141.2007.06924.x|issn=1365-2141|pmid=18275429}}</ref>

*See other sections.

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==Gene Mutations (SNV / INDEL)==

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!Gene

*Uncommon: FAS, STIM2<ref name=":2" />; LRP1B (9%), EPHA5<ref name=":6" />

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==Epigenomic Alterations==

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*JAK-STAT<ref name=":2" />

**When ''JAK/STAT3'' mutations absent, ''NFkB2-ROS1'' and ''NFkB2-TYK2'' fusions may constitutively activate STAT pathway

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==Genetic Diagnostic Testing Methods==