HAEM5:NK-large granular lymphocytic leukaemia: Difference between revisions

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

Hailee St. Louis, MD, UC San Diego

==WHO Classification of Disease==

|Category

|T-cell and NK-cell lymphoid proliferations and lymphomas

|Family

|Mature T-cell and NK-cell neoplasms

|Type

|Mature T-cell and NK-cell leukaemias

|Subtype(s)

|NK-large granular lymphocytic leukaemia

|}

 

|Not Recommended

|Chronic NK-cell lymphocytosis; indolent leukaemia of NK cells

|}

!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)

!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|N/A

|N/A

|N/A

|N/A

|N/A

|N/A

|N/A

|N/A

|}

!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|N/A

|N/A

|N/A

|N/A

|N/A

|N/A

|N/A

!Molecular Pathogenesis

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|N/A

|N/A

|N/A

|N/A

|}

!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|''STAT3''

|Exons 12-21 encoding the Src homology 2 (SH2 domain on two hotspots: D661 and Y640), driver mutation <ref name=":1">{{Cite journal|last=Rajala|first=Hanna L. M.|last2=Eldfors|first2=Samuli|last3=Kuusanmäki|first3=Heikki|last4=van Adrichem|first4=Arjan J.|last5=Olson|first5=Thomas|last6=Lagström|first6=Sonja|last7=Andersson|first7=Emma I.|last8=Jerez|first8=Andres|last9=Clemente|first9=Michael J.|date=2013-05-30|title=Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/23596048|journal=Blood|volume=121|issue=22|pages=4541–4550|doi=10.1182/blood-2012-12-474577|issn=1528-0020|pmc=3668487|pmid=23596048}}</ref>

|No

|Specific to NK-LGL <ref name=":3" />

|Recurrent: 6% <ref name=":9">{{Cite journal|last=Kawakami|first=Toru|last2=Sekiguchi|first2=Nodoka|last3=Kobayashi|first3=Jun|last4=Yamane|first4=Taku|last5=Nishina|first5=Sayaka|last6=Sakai|first6=Hitoshi|last7=Hirabayashi|first7=Yukio|last8=Nakazawa|first8=Hideyuki|last9=Ishida|first9=Fumihiro|date=2019-05|title=STAT3 mutations in natural killer cells are associated with cytopenia in patients with chronic lymphoproliferative disorder of natural killer cells|url=https://pubmed.ncbi.nlm.nih.gov/30859397|journal=International Journal of Hematology|volume=109|issue=5|pages=563–571|doi=10.1007/s12185-019-02625-x|issn=1865-3774|pmid=30859397}}</ref> - 10% <ref name=":4" />

(NK-LGL)

|''PI3K'' pathway genes

|PIK3CD activating mutation, PIK3AP1 mutation not previously described <ref name=":5" />

|

|Rare: 3 patients (5%) <ref name=":5" />

(NK-LGL)

|''STAT5b''

|Exon 16 missense N642H mutation in the SH2 domain, driver mutation <ref name=":1" />

|Rare: 1 patient <ref name=":1" />

|No

|Progressed to aggressive disease and died due to disease <ref name=":1" />

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

|''STAT3;'' gain of function mutations

|''TET2''; loss of function mutations

|DNA methylation/epigenetic regulation

|DNA methylation alters NK cell gene expression<ref>{{Cite journal|last=Semenzato|first=Gianpietro|last2=Teramo|first2=Antonella|last3=Barilà|first3=Gregorio|last4=Calabretto|first4=Giulia|last5=Rampazzo|first5=Elisa|last6=Buson|first6=Elena|last7=Zambello|first7=Renato|date=2025-06|title=NK-type large granular lymphocyte leukemia comes of age|url=https://pubmed.ncbi.nlm.nih.gov/40568352|journal=HemaSphere|volume=9|issue=6|pages=e70161|doi=10.1002/hem3.70161|issn=2572-9241|pmc=12194722|pmid=40568352}}</ref>

|''CCL22''; gain of function mutations

|Chemokine signaling and microenvironmental interaction

|Alters NK cell interaction with the microenvironment, contributing to clonal dominance and unique immunophenotype <ref name=":6" />

|''TNFAIP3''; inactivating alterations

|NF-κB negative regulation

|Loss of negative regulation enhances NF-κB signaling, promoting cell survival and anti-apoptotic transcription<ref name=":4" />

|''KRAS, NOTCH1'' ''PTEN; PIK3R1'', ''PIK3CD,''  PIK3AP1

|RAS/MAPK and Pi3K/AKT pathways

|Dysregulation of the balance between survival and apoptosis <ref name=":8" /><ref name=":3" />

 

*Assessing for restricted expression of KIR isoforms, is often used as a surrogate for clonality <ref name=":7">{{Cite journal|last=Lamy|first=Thierry|last2=Moignet|first2=Aline|last3=Loughran|first3=Thomas P.|date=2017-03-02|title=LGL leukemia: from pathogenesis to treatment|url=https://pubmed.ncbi.nlm.nih.gov/28115367|journal=Blood|volume=129|issue=9|pages=1082–1094|doi=10.1182/blood-2016-08-692590|issn=1528-0020|pmid=28115367}}</ref>.

 

*Absence of T-cell receptor gene rearrangements by PCR<ref name=":7" />.

 

 

 

 

N/A

<references />

<nowiki>*</nowiki>''Citation of this Page'': St. Louis H, Don M. “NK-large granular lymphocytic leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:NK-large_granular_lymphocytic_leukaemia</nowiki>.

 

<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 [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

 

Prior Author(s):

[[Category:HAEM5]]

[[Category:DISEASE]]

[[Category:Diseases N]]