HAEM5:Aggressive NK-cell leukaemia: Difference between revisions

[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]

<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). 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>

Shanelle De Lancy, MD, Shashirekha Shetty, PhD

|'''Signs and Symptoms'''

|EXAMPLE Asymptomatic (incidental finding on complete blood counts)

EXAMPLE Lymphadenopathy (uncommon)

|'''Laboratory Findings'''

|EXAMPLE Cytopenias

 

 

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<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>{{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>

 

 

 

 

 

 

 

 

 

 

 

 

 

 

==Immunophenotype==

 

 

!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)==

 

!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence

|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)

|Yes

|Yes

|EXAMPLE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

{| class="wikitable sortable"

!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)

|EXAMPLE

 

7

|EXAMPLE Loss

|EXAMPLE

 

chr7:1- 159,335,973 [hg38]

 

|Yes

|EXAMPLE

 

|EXAMPLE

 

|EXAMPLE Gain

|EXAMPLE

 

chr8:1-145,138,636 [hg38]

|EXAMPLE

 

|No

|EXAMPLE

 

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

|1q23.1-q23.2

|Gain

|1q31.3-q44

|Gain

|7p15.1-q22.3

|Loss

|-

|17p13.1

|Loss

|}

 

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!Chromosomal Pattern

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|EXAMPLE

Co-deletion of 1p and 18q

|Yes

|No

|No

|EXAMPLE:

 

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

|}

 

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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.  

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==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; 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.'') </span>

!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)'''

|EXAMPLE: TP53; Variable LOF mutations

 

 

 

|EXAMPLE: TSG

|EXAMPLE: 20% (COSMIC)

 

|EXAMPLE: IDH1 R123H

|EXAMPLE: EGFR amplification

|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).

|Tumor suppressor

 

*Mutations in the ''JAK-STAT'' pathway appear to be mutually exclusive<ref name=":3">{{Cite journal|last=Huang|first=Liang|last2=Liu|first2=Dan|last3=Wang|first3=Na|last4=Ling|first4=Shaoping|last5=Tang|first5=Yuting|last6=Wu|first6=Jun|last7=Hao|first7=Lingtong|last8=Luo|first8=Hui|last9=Hu|first9=Xuelian|date=2018-02|title=Integrated genomic analysis identifies deregulated JAK/STAT-MYC-biosynthesis axis in aggressive NK-cell leukemia|url=http://www.nature.com/articles/cr2017146|journal=Cell Research|language=en|volume=28|issue=2|pages=172–186|doi=10.1038/cr.2017.146|issn=1001-0602|pmc=PMC5799812|pmid=29148541}}</ref>

*Most ''STAT3'' and ''STAT5B''  mutations localized to exons 20 and 21 encoding the Src homology 2 (SH2) domain, which causes ''STAT'' dimerization

*Other mutations identified:  

**point mutation in protein tyrosine phosphatase (''PTPRK'') (tumor suppressor that negatively regulates ''STAT3'')

**mutations in ''PTPN4'' and ''PTPN23''

 

 

 

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Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>

|EXAMPLE: BRAF and MAP2K1; Activating mutations

|EXAMPLE: MAPK signaling

|EXAMPLE: Increased cell growth and proliferation

|EXAMPLE: CDKN2A; Inactivating mutations

|EXAMPLE: Cell cycle regulation

|EXAMPLE: Unregulated cell division

|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations

|EXAMPLE:  Histone modification, chromatin remodeling

|EXAMPLE:  Abnormal gene expression program

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*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'')

<nowiki>*</nowiki>Thought in some cases to be as a result of highly expressed EBV-encoded small RNAs (EBERs) causing release of IL-10.

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Foundation of diagnosis based on morphology with immunophenotyping via flow cytometry +/- immunohistochemistry.

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N/A

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

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

(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''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.''</span> <span style="color:#0070C0">''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''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />

<nowiki>*</nowiki>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.

[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases A]]