HAEM5:NK-large granular lymphocytic leukaemia: Difference between revisions
| [unchecked revision] | [unchecked revision] |
| Line 8: | Line 8: | ||
}}</blockquote> | }}</blockquote> | ||
< | <br /> | ||
==Primary Author(s)*== | ==Primary Author(s)*== | ||
| Line 34: | Line 34: | ||
==Synonyms / Terminology== | ==Synonyms / Terminology== | ||
* Chronic lymphoproliferative disorder of NK cells | *Chronic lymphoproliferative disorder of NK cells | ||
* Chronic NK-large granular lymphocyte lymphoproliferative disorder | *Chronic NK-large granular lymphocyte lymphoproliferative disorder | ||
* Chronic NK-cell lymphocytosis (historical) | *Chronic NK-cell lymphocytosis (historical) | ||
* Indolent leukemia of NK cells (historical) <ref name=":0" /> | *Indolent leukemia of NK cells (historical) <ref name=":0" /> | ||
==Epidemiology / Prevalence== | ==Epidemiology / Prevalence== | ||
* Median age: 60 years | *Median age: 60 years | ||
* Does not show sex, racial, geographical, or genetic predisposition <ref name=":0" /> | *Does not show sex, racial, geographical, or genetic predisposition <ref name=":0" /> | ||
==Clinical Features== | ==Clinical Features== | ||
| Line 62: | Line 62: | ||
==Sites of Involvement== | ==Sites of Involvement== | ||
* Peripheral blood and bone marrow | *Peripheral blood and bone marrow | ||
* Uncommon: spleen <ref name=":0" /> | *Uncommon: spleen <ref name=":0" /> | ||
==Morphologic Features== | ==Morphologic Features== | ||
* NK-cells are typically intermediate to large in size with small, round nuclei and moderate cytoplasm with fine or coarse azurophilic granules. | *NK-cells are typically intermediate to large in size with small, round nuclei and moderate cytoplasm with fine or coarse azurophilic granules. | ||
* Intrasinusoidal and sometimes interstitial infiltration of bone marrow and possibly spleen. <ref name=":0" /> | *Intrasinusoidal and sometimes interstitial infiltration of bone marrow and possibly spleen. <ref name=":0" /> | ||
==Immunophenotype <ref name=":0" />== | ==Immunophenotype <ref name=":0" />== | ||
| Line 121: | Line 121: | ||
!Notes | !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> | |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> | ||
| | | | ||
|Variable: 9% <ref>{{Cite journal|last=Gasparini|first=Vanessa Rebecca|last2=Binatti|first2=Andrea|last3=Coppe|first3=Alessandro|last4=Teramo|first4=Antonella|last5=Vicenzetto|first5=Cristina|last6=Calabretto|first6=Giulia|last7=Barilà|first7=Gregorio|last8=Barizza|first8=Annica|last9=Giussani|first9=Edoardo|date=2020-04-22|title=A high definition picture of somatic mutations in chronic lymphoproliferative disorder of natural killer cells|url=https://pubmed.ncbi.nlm.nih.gov/32321919|journal=Blood Cancer Journal|volume=10|issue=4|pages=42|doi=10.1038/s41408-020-0309-2|issn=2044-5385|pmc=7176632|pmid=32321919}}</ref> to 30% <ref name=":2">{{Cite journal|last=Jerez|first=Andres|last2=Clemente|first2=Michael J.|last3=Makishima|first3=Hideki|last4=Koskela|first4=Hanna|last5=Leblanc|first5=Francis|last6=Peng Ng|first6=Kwok|last7=Olson|first7=Thomas|last8=Przychodzen|first8=Bartlomiej|last9=Afable|first9=Manuel|date=2012-10-11|title=STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia|url=https://pubmed.ncbi.nlm.nih.gov/22859607|journal=Blood|volume=120|issue=15|pages=3048–3057|doi=10.1182/blood-2012-06-435297|issn=1528-0020|pmc=3471515|pmid=22859607}}</ref> | |Variable: 9% <ref>{{Cite journal|last=Gasparini|first=Vanessa Rebecca|last2=Binatti|first2=Andrea|last3=Coppe|first3=Alessandro|last4=Teramo|first4=Antonella|last5=Vicenzetto|first5=Cristina|last6=Calabretto|first6=Giulia|last7=Barilà|first7=Gregorio|last8=Barizza|first8=Annica|last9=Giussani|first9=Edoardo|date=2020-04-22|title=A high definition picture of somatic mutations in chronic lymphoproliferative disorder of natural killer cells|url=https://pubmed.ncbi.nlm.nih.gov/32321919|journal=Blood Cancer Journal|volume=10|issue=4|pages=42|doi=10.1038/s41408-020-0309-2|issn=2044-5385|pmc=7176632|pmid=32321919}}</ref> to 30% <ref name=":2">{{Cite journal|last=Jerez|first=Andres|last2=Clemente|first2=Michael J.|last3=Makishima|first3=Hideki|last4=Koskela|first4=Hanna|last5=Leblanc|first5=Francis|last6=Peng Ng|first6=Kwok|last7=Olson|first7=Thomas|last8=Przychodzen|first8=Bartlomiej|last9=Afable|first9=Manuel|date=2012-10-11|title=STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia|url=https://pubmed.ncbi.nlm.nih.gov/22859607|journal=Blood|volume=120|issue=15|pages=3048–3057|doi=10.1182/blood-2012-06-435297|issn=1528-0020|pmc=3471515|pmid=22859607}}</ref> | ||
| Line 139: | Line 139: | ||
|Yes | |Yes | ||
|Unknown | |Unknown | ||
|Resistance to immunosuppressive agents have been observed; no current therapeutic target <ref name=":5" /> | |Resistance to immunosuppressive agents have been observed; no current therapeutic target <ref name=":5" /> | ||
| - Also seen in T-LGL | | - Also seen in T-LGL | ||
- Commonly associated with CD16 low phenotype | - Commonly associated with CD16 low phenotype | ||
| Line 190: | Line 190: | ||
==Epigenomic Alterations== | ==Epigenomic Alterations== | ||
* TET2 shows increased methylated regions in clonal NK-LGLs compared to normal NK-cells <ref name=":5" /> | *TET2 shows increased methylated regions in clonal NK-LGLs compared to normal NK-cells <ref name=":5" /> | ||
==Genes and Main Pathways Involved== | ==Genes and Main Pathways Involved== | ||
| Line 197: | Line 197: | ||
==Genetic Diagnostic Testing Methods== | ==Genetic Diagnostic Testing Methods== | ||
* 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>. | *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>. | ||
* Mutational screen for STAT3, STAT5b, TET2, TNFAIP3 and CCL22 mutations may be more helpful when compared to KIR analysis on diagnostic work-up <ref name=":3" />. | *Mutational screen for STAT3, STAT5b, TET2, TNFAIP3 and CCL22 mutations may be more helpful when compared to KIR analysis on diagnostic work-up <ref name=":3" />. | ||
* Absence of T-cell receptor gene rearrangement studies <ref name=":7" />. | *Absence of T-cell receptor gene rearrangement studies <ref name=":7" />. | ||
* Sanger Sequencing. | *Sanger Sequencing. | ||
* Whole Genome Sequencing. | *Whole Genome Sequencing. | ||
==Familial Forms== | ==Familial Forms== | ||