HAEM5:Aggressive NK-cell leukaemia: Difference between revisions

<blockquote class="blockedit">{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Aggressive NK-cell Leukemia]].

<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>

==Definition / Description of Disease==

|'''Signs and Symptoms'''

|Constitutional symptoms (weight loss, fever, night sweats)

 

 

|'''Laboratory Findings'''

|Markedly elevated serum lactate dehydrogenase (LDH) levels

Variable percentage of circulating leukemic cells

Anemia, neutropenia, thrombocytopenia

 

<blockquote class="blockedit">{{Box-round|title=v4:Clinical Features|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}

 

 

 

 

 

 

 

<nowiki>*</nowiki>EBV-negative cases may occur ''de novo'' or transform from chronic lymphoproliferative disorder of NK cells

 

 

<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":4">{{Cite journal|last=Kim|first=Wook Youn|last2=Montes-Mojarro|first2=Ivonne A.|last3=Fend|first3=Falko|last4=Quintanilla-Martinez|first4=Leticia|date=2019|title=Epstein-Barr Virus-Associated T and NK-Cell Lymphoproliferative Diseases|url=https://pubmed.ncbi.nlm.nih.gov/30931288|journal=Frontiers in Pediatrics|volume=7|pages=71|doi=10.3389/fped.2019.00071|issn=2296-2360|pmc=6428722|pmid=30931288}}</ref></blockquote>

 

 

 

 

 

 

 

 

 

 

 

 

 

!Finding!!Marker

|Positive (universal)||CD2, CD3-epsilon, CD56, CD94, cytotoxic molecules (TIA1, Granzyme B, perforin A), FASL, c-MYC

|Positive (subset)||CD16 (75%), CD11b, EBER, p53, pSTAT3, PD-L1, BCL2

|Negative (universal)||surface CD3, CD4, CD5, CD57 (usually), CD158a/b/e, TCR alpha/beta, TCR gamma/delta

|Negative (subset)||CD7, CD45

 

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==Chromosomal Rearrangements (Gene Fusions)==

 

Due to the rarity of this lymphoma the data in recurrent chromosomal rearrangement is extremely scant. There have been chromosomal rearrangements reported in association with the aggressive NK-cell leukaemia, however, none of them are considered specific for the disease.

 

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<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:

* Chromosomal Rearrangements (Gene Fusions)

 

 

Molecular abnormalities present possible therapeutic implications.  

 

Dufva et al identified high sensitivity of ANKL cell lines to JAK and BCL2 inhibition.

 

Other possibly effective drug classes:

 

*Polo-like kinase (PLK) inhibitors

 

 

<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":6">{{Cite journal|last=Dufva|first=Olli|last2=Kankainen|first2=Matti|last3=Kelkka|first3=Tiina|last4=Sekiguchi|first4=Nodoka|last5=Awad|first5=Shady Adnan|last6=Eldfors|first6=Samuli|last7=Yadav|first7=Bhagwan|last8=Kuusanmäki|first8=Heikki|last9=Malani|first9=Disha|date=04 19, 2018|title=Aggressive natural killer-cell leukemia mutational landscape and drug profiling highlight JAK-STAT signaling as therapeutic target|url=https://pubmed.ncbi.nlm.nih.gov/29674644|journal=Nature Communications|volume=9|issue=1|pages=1567|doi=10.1038/s41467-018-03987-2|issn=2041-1723|pmc=5908809|pmid=29674644}}</ref></blockquote>

 

There have been a few chromosomal abnormalities associated with aggressive NK-cell leukaemia as listed below, however, the specificity along with prognostic and therapeutic significance is unknown.<ref name=":2" />

<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}

!Chromosome!!Gain/Loss/Amp/LOH<br />

|1q23.1-q23.2

|Gain

|1q31.3-q44

|Gain

|7p15.1-q22.3

|Loss

|-

|17p13.1

|Loss

|}

 

<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":0" /><ref name=":1" /></blockquote>

 

!Chromosomal Pattern

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|}

<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}

 

 

Due to rare nature of disease, cytogenetics data is limited. However, common abnormalities include del(6)(q21q25) and del(11q).

 

Complex karyotypes with unbalanced rearrangements are frequently seen.  

 

Molecular abnormalities present possible therapeutic implications. Dufva et al identified high sensitivity of ANKL cell lines to JAK and BCL2 inhibition. Other possibly effective drug classes are heat shock protein 90 (HSP90) inhibitors, polo-like kinase (PLK) inhibitors, aurora kinase (AURK) inhibitors, cyclin-dependent kinase inhibitors, and histone deacetylase inhibitors.<ref name=":6" />

!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)'''

 

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<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}

*Upregulated JAK/STAT-MYC biosynthesis axis due to upstream STAT3 activation of the MYC transcription program. *

*Epigenetic modifier genes (e.g ''BCOR, KMT2D/MLL2'', ''SETD2'', ''PRDM9'', ''CREBBP'', and ''TET2'')

*DNA damage repair (''TP53, ASXL1, ASXL2, BRINP3)''

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</blockquote>

Foundation of diagnosis based on morphology with immunophenotyping via flow cytometry +/- immunohistochemistry.<ref name=":0" />

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N/A

[[Hepatosplenic T-cell Lymphoma (HSTCL)]]

[[Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK)]]

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