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Chronic lymphoproliferative disorder of NK-cells

MedGen UID:
268922
•Concept ID:
C1512709
•
Neoplastic Process
Synonyms: Chronic lymphoproliferative disorder of natural killer cells; chronic lymphoproliferative disorder of natural killer cells; Chronic Lymphoproliferative Disorder of NK-Cells; chronic lymphoproliferative disorder of NK-cells; Chronic NK lymphocytosis; chronic NK lymphocytosis; Chronic NK-Cell Lymphocytosis; chronic NK-cell lymphocytosis; Chronic NK-cell lymphocytosis; Chronic NK-Large Granular Lymphocyte Lymphoproliferative Disorder; chronic NK-large granular lymphocyte lymphoproliferative disorder; Chronic NK-LGL Lymphoproliferative Disorder; chronic NK-LGL lymphoproliferative disorder; CLPD-NK; CNKL; Indolent Large Granular NK-Cell Lymphoproliferative Disorder; indolent large granular NK-cell lymphoproliferative disorder; Indolent NK-Cell Lymphoproliferative Disorder; indolent NK-cell lymphoproliferative disorder; natural killer-cell large granular lymphocyte leukaemia; natural killer-cell large granular lymphocyte leukemia; NK-Cell Large Granular Lymphocyte Lymphocytosis; NK-cell large granular lymphocyte lymphocytosis; NK-cell lineage granular lymphocyte proliferative disorder; NK-LGL leukaemia; NK-LGL leukemia; NK-LGLL; NK-Type Lymphoproliferative Disorder of Granular Lymphocytes; NK-type lymphoproliferative disorder of granular lymphocytes
SNOMED CT: Chronic lymphoproliferative disorder of natural killer cells (722955006); Chronic lymphoproliferative disorder of NK-cells (722955006)
 
Monarch Initiative: MONDO:0004234
Orphanet: ORPHA512017

Definition

A rare large granular lymphocyte leukemia characterized by persistent (> 6 months) natural killer cell lymphocytosis in the absence of clinical diagnosis of leukemia/lymphoma, autoimmune disease, or chronic viral infections. The clinical course is variable, but generally indolent. Patients often remain asymptomatic, or may present with clinical manifestations including vasculitic skin lesions, neutropenic infections, musculoskeletal symptoms, peripheral neuropathy, or splenomegaly. [from ORDO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVChronic lymphoproliferative disorder of NK-cells

Professional guidelines

PubMed

Large Granular Lymphocytic Leukemia: Current State of Diagnosis, Pathogenesis and Treatment.
Magnano L, Rivero A, Matutes E
Curr Oncol Rep 2022 May;24(5):633-644. Epub 2022 Feb 25 doi: 10.1007/s11912-021-01159-y. PMID: 35212923
Latest Advances in the Diagnosis and Treatment of Large Granular Lymphocytic Leukemia.
Moignet A, Lamy T
Am Soc Clin Oncol Educ Book 2018 May 23;38:616-625. doi: 10.1200/EDBK_200689. PMID: 30231346
The pathogenesis and treatment of large granular lymphocyte leukemia.
Steinway SN, LeBlanc F, Loughran TP Jr
Blood Rev 2014 May;28(3):87-94. Epub 2014 Mar 7 doi: 10.1016/j.blre.2014.02.001. PMID: 24679833Free PMC Article

Recent clinical studies

Etiology

Frequent somatic TET2 mutations in chronic NK-LGL leukemia with distinct patterns of cytopenias.
Olson TL, Cheon H, Xing JC, Olson KC, Paila U, Hamele CE, Neelamraju Y, Shemo BC, Schmachtenberg M, Sundararaman SK, Toro MF, Keller CA, Farber EA, Onengut-Gumuscu S, Garrett-Bakelman FE, Hardison RC, Feith DJ, Ratan A, Loughran TP
Blood 2021 Aug 26;138(8):662-673. doi: 10.1182/blood.2020005831. PMID: 33786584Free PMC Article
Linking the KIR phenotype with STAT3 and TET2 mutations to identify chronic lymphoproliferative disorders of NK cells.
Pastoret C, Desmots F, Drillet G, Le Gallou S, Boulland ML, Thannberger A, Doncker AV, Salaun V, Damaj GL, Veyrat-Masson R, Tournilhac O, Moignet A, Pangault C, Roussel M, Fest T, Lamy T
Blood 2021 Jun 10;137(23):3237-3250. doi: 10.1182/blood.2020006721. PMID: 33512451Free PMC Article
Chronic lymphoproliferative disorder of NK-cells: A single-institution review with emphasis on relative utility of multimodality diagnostic tools.
Kurt H, Jorgensen JL, Amin HM, Patel KP, Wang SA, Lin P, Kanagal-Shamanna R, Loghavi S, Thakral B, Khogeer HA, Jabbour EJ, Li S, Yin CC, Medeiros LJ, Khoury JD
Eur J Haematol 2018 May;100(5):444-454. Epub 2018 Mar 9 doi: 10.1111/ejh.13038. PMID: 29385279
Detection of monoclonal T populations in patients with KIR-restricted chronic lymphoproliferative disorder of NK cells.
Gattazzo C, Teramo A, Passeri F, De March E, Carraro S, Trimarco V, Frezzato F, Berno T, Barilà G, Martini V, Piazza F, Trentin L, Facco M, Semenzato G, Zambello R
Haematologica 2014 Dec;99(12):1826-33. Epub 2014 Sep 5 doi: 10.3324/haematol.2014.105726. PMID: 25193965Free PMC Article
State of the art in natural killer cell malignancies.
Semenzato G, Marino F, Zambello R
Int J Lab Hematol 2012 Apr;34(2):117-28. Epub 2011 Sep 6 doi: 10.1111/j.1751-553X.2011.01374.x. PMID: 21895989

Diagnosis

Genomic landscape of T-large granular lymphocyte leukemia and chronic lymphoproliferative disorder of NK cells: a single institution experience.
Fei F, Stehr H, Zehnder JL
Leuk Lymphoma 2023 Sep;64(9):1536-1544. Epub 2023 Jun 17 doi: 10.1080/10428194.2023.2220450. PMID: 37330635
Large granular lymphocyte leukaemia study at the University Hospital of Donostia.
Uranga A, González C, Furundarena JR, Robado N, Rey M, Aragon L, Urreta I, Aranbarri A, De Juan MD, Araiz M
J Clin Pathol 2022 Apr;75(4):226-233. Epub 2021 Jan 21 doi: 10.1136/jclinpath-2020-207191. PMID: 33479020
Linking the KIR phenotype with STAT3 and TET2 mutations to identify chronic lymphoproliferative disorders of NK cells.
Pastoret C, Desmots F, Drillet G, Le Gallou S, Boulland ML, Thannberger A, Doncker AV, Salaun V, Damaj GL, Veyrat-Masson R, Tournilhac O, Moignet A, Pangault C, Roussel M, Fest T, Lamy T
Blood 2021 Jun 10;137(23):3237-3250. doi: 10.1182/blood.2020006721. PMID: 33512451Free PMC Article
Chronic lymphoproliferative disorder of NK-cells: A single-institution review with emphasis on relative utility of multimodality diagnostic tools.
Kurt H, Jorgensen JL, Amin HM, Patel KP, Wang SA, Lin P, Kanagal-Shamanna R, Loghavi S, Thakral B, Khogeer HA, Jabbour EJ, Li S, Yin CC, Medeiros LJ, Khoury JD
Eur J Haematol 2018 May;100(5):444-454. Epub 2018 Mar 9 doi: 10.1111/ejh.13038. PMID: 29385279
Detection of monoclonal T populations in patients with KIR-restricted chronic lymphoproliferative disorder of NK cells.
Gattazzo C, Teramo A, Passeri F, De March E, Carraro S, Trimarco V, Frezzato F, Berno T, Barilà G, Martini V, Piazza F, Trentin L, Facco M, Semenzato G, Zambello R
Haematologica 2014 Dec;99(12):1826-33. Epub 2014 Sep 5 doi: 10.3324/haematol.2014.105726. PMID: 25193965Free PMC Article

Therapy

Oral cyclophosphamide was effective for Coombs-negative autoimmune hemolytic anemia in CD16+CD56- chronic lymphoproliferative disorder of NK-cells.
Sekiguchi N, Nishina S, Kawakami T, Sakai H, Senoo N, Senoo Y, Ito T, Saito H, Nakazawa H, Koizumi T, Ishida F
Int J Hematol 2017 Jun;105(6):854-858. Epub 2016 Dec 27 doi: 10.1007/s12185-016-2170-4. PMID: 28028749

Prognosis

Large granular lymphocyte leukaemia study at the University Hospital of Donostia.
Uranga A, González C, Furundarena JR, Robado N, Rey M, Aragon L, Urreta I, Aranbarri A, De Juan MD, Araiz M
J Clin Pathol 2022 Apr;75(4):226-233. Epub 2021 Jan 21 doi: 10.1136/jclinpath-2020-207191. PMID: 33479020
Linking the KIR phenotype with STAT3 and TET2 mutations to identify chronic lymphoproliferative disorders of NK cells.
Pastoret C, Desmots F, Drillet G, Le Gallou S, Boulland ML, Thannberger A, Doncker AV, Salaun V, Damaj GL, Veyrat-Masson R, Tournilhac O, Moignet A, Pangault C, Roussel M, Fest T, Lamy T
Blood 2021 Jun 10;137(23):3237-3250. doi: 10.1182/blood.2020006721. PMID: 33512451Free PMC Article
Chronic lymphoproliferative disorder of NK-cells: A single-institution review with emphasis on relative utility of multimodality diagnostic tools.
Kurt H, Jorgensen JL, Amin HM, Patel KP, Wang SA, Lin P, Kanagal-Shamanna R, Loghavi S, Thakral B, Khogeer HA, Jabbour EJ, Li S, Yin CC, Medeiros LJ, Khoury JD
Eur J Haematol 2018 May;100(5):444-454. Epub 2018 Mar 9 doi: 10.1111/ejh.13038. PMID: 29385279
Detection of monoclonal T populations in patients with KIR-restricted chronic lymphoproliferative disorder of NK cells.
Gattazzo C, Teramo A, Passeri F, De March E, Carraro S, Trimarco V, Frezzato F, Berno T, Barilà G, Martini V, Piazza F, Trentin L, Facco M, Semenzato G, Zambello R
Haematologica 2014 Dec;99(12):1826-33. Epub 2014 Sep 5 doi: 10.3324/haematol.2014.105726. PMID: 25193965Free PMC Article
State of the art in natural killer cell malignancies.
Semenzato G, Marino F, Zambello R
Int J Lab Hematol 2012 Apr;34(2):117-28. Epub 2011 Sep 6 doi: 10.1111/j.1751-553X.2011.01374.x. PMID: 21895989

Clinical prediction guides

Frequent somatic TET2 mutations in chronic NK-LGL leukemia with distinct patterns of cytopenias.
Olson TL, Cheon H, Xing JC, Olson KC, Paila U, Hamele CE, Neelamraju Y, Shemo BC, Schmachtenberg M, Sundararaman SK, Toro MF, Keller CA, Farber EA, Onengut-Gumuscu S, Garrett-Bakelman FE, Hardison RC, Feith DJ, Ratan A, Loughran TP
Blood 2021 Aug 26;138(8):662-673. doi: 10.1182/blood.2020005831. PMID: 33786584Free PMC Article
Linking the KIR phenotype with STAT3 and TET2 mutations to identify chronic lymphoproliferative disorders of NK cells.
Pastoret C, Desmots F, Drillet G, Le Gallou S, Boulland ML, Thannberger A, Doncker AV, Salaun V, Damaj GL, Veyrat-Masson R, Tournilhac O, Moignet A, Pangault C, Roussel M, Fest T, Lamy T
Blood 2021 Jun 10;137(23):3237-3250. doi: 10.1182/blood.2020006721. PMID: 33512451Free PMC Article
Chronic lymphoproliferative disorder of NK-cells: A single-institution review with emphasis on relative utility of multimodality diagnostic tools.
Kurt H, Jorgensen JL, Amin HM, Patel KP, Wang SA, Lin P, Kanagal-Shamanna R, Loghavi S, Thakral B, Khogeer HA, Jabbour EJ, Li S, Yin CC, Medeiros LJ, Khoury JD
Eur J Haematol 2018 May;100(5):444-454. Epub 2018 Mar 9 doi: 10.1111/ejh.13038. PMID: 29385279
Seroreactivity to an envelope protein of human T-cell leukemia/lymphoma virus in patients with CD3- (natural killer) lymphoproliferative disease of granular lymphocytes.
Loughran TP Jr, Hadlock KG, Yang Q, Perzova R, Zambello R, Semenzato G, Foung SK, Poiesz BJ
Blood 1997 Sep 1;90(5):1977-81. PMID: 9292532

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