Difference between revisions of "HAEM5:T-large granular lymphocytic leukaemia"

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Haematolymphoid Tumours (WHO Classification, 5th ed.)

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editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:T-cell Large Granular Lymphocytic Leukemia.

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), 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 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 Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

Michelle Don, MD, MS

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
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)	T-large granular lymphocytic leukaemia

Definition / Description of Disease

Increased peripheral blood large granular lymphocytes (LGLs) for >6 months without a identifiable cause
Chronic and often indolent T-cell proliferation

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^[1]

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Synonyms / Terminology

T-cell large granular lymphocytic leukemia

Epidemiology / Prevalence

2-3% of mature small lymphocytic leukemias
Male:Female ~ 1:1
Most commonly occurs between ages 45-75 years old

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^[1]

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Clinical Features

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)

Signs and Symptoms	EXAMPLE: Asymptomatic (incidental finding on complete blood counts) EXAMPLE: B-symptoms (weight loss, fever, night sweats) EXAMPLE: Fatigue EXAMPLE: Lymphadenopathy (uncommon)
Laboratory Findings	EXAMPLE: Cytopenias EXAMPLE: Lymphocytosis (low level)

editv4:Clinical Features

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Severe neutropenia
Lymphocyte count usually 2-20x10⁹/L
Has been reported to occur with:
- Severe red cell hypoplasia
- Rheumatoid arthritis
- Low grade B-cell malignancies

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^[1]

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Sites of Involvement

Peripheral blood and bone marrow
Spleen - infiltration and expansion of red pulp
Liver
Skin (rare)
Lymph nodes (exceptional)

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^[1]

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Morphologic Features

Large granular lymphocytes

Moderate to abundant cytoplasm
Fine or course azurophilic granules

Immunophenotype

Finding	Marker
Positive	CD8, CD2, CD3, CD16, CD57, αβ (alpha-beta) TCR Cytotoxic effector proteins: TIA1, Granzyme B, Granzyme M
Negative	CD4, CD5, CD7
Please note:	Cases of CD4+ LGL leukemia has been described^[2] Cases of CD4-/CD8-, γδ (gamma-delta) T-LGL leukemia has also been described (<5% of cases)^[3]

editUnassigned References

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^[1]

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Chromosomal Rearrangements (Gene Fusions)

Put your text here and fill in the table

Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: t(9;22)(q34;q11.2)	EXAMPLE: 3'ABL1 / 5'BCR	EXAMPLE: der(22)	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add reference)	Yes	No	Yes	EXAMPLE: The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).

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No known chromosomal rearrangements

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editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).

Please incorporate this section into the relevant tables found in:
Chromosomal Rearrangements (Gene Fusions)

Individual Region Genomic Gain/Loss/LOH

Characteristic Chromosomal Patterns

Gene Mutations (SNV/INDEL)

There are no FDA approved targeted therapies for T-LGL
STAT3 mutations can be used to follow-up, in response to treatment^[4]
- Take caution as STAT mutations are not specific to T-LGL and can be seen in other T-cell lymphomas
STAT3 mutation, Y640F, has a predicted response to initial therapy with methotrexate^[5]
Bortezomib is considered due to NF-κB constitutive activity in T-LGL leukemia^[6]

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Individual Region Genomic Gain / Loss / LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.)

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)	Notes
EXAMPLE: 7	EXAMPLE: Loss	EXAMPLE: chr7:1- 159,335,973 [hg38]	EXAMPLE: chr7	Yes	Yes	No	EXAMPLE: Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
EXAMPLE: 8	EXAMPLE: Gain	EXAMPLE: chr8:1-145,138,636 [hg38]	EXAMPLE: chr8	No	No	No	EXAMPLE: Common recurrent secondary finding for t(8;21) (add reference).

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No known recurrent copy number gain/loss/LOH, chromosomal abnormalities have been reported in few cases^[7]

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Characteristic Chromosomal Patterns

Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis. Do not delete table.)

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).

editv4:Characteristic Chromosomal Aberrations / Patterns

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No characteristic chromosomal aberrations have been identified
Unique cytogenetic findings include: (reported in one case report of γδ variant T-cell LGL)^[8]
- Interstitial deletion of 3p21.31, monosomy X, trisomy 5, monosomy 21, and CN‐LOH located at 17q^[8]

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Gene Mutations (SNV / INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as 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. Do not delete table.)

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)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: TP53; Variable LOF mutations EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations	EXAMPLE: TSG	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add Reference)	EXAMPLE: IDH1 R123H	EXAMPLE: EGFR amplification				EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

editv4:Gene Mutations (SNV/INDEL)

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Somatic activating STAT3 and STAT5b mutations are the most common SNVs in T-LGL.

Gene*	Mutation	Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)	Prevalence	Additional information
STAT3	Src-like homologue 2 (SH2) domain of STAT3 Most frequently affecting codons Y640 or D661^[1] Also affecting: N647I^[9] K658S^[9] Causing constitutive phosphorylation of the mutated proteins, and increased the transcriptional activity of STAT3 in vitro^[10]^[11]	GOF	40-70%^[11]	17% of patients with STAT3 mutations, had multiple mutations in the STAT3 gene, solely in cytotoxic CD8+ or NK cells.^[4] Take caution as STAT3 mutation can also be seen in other T-cell lymphomas including hepatosplenic T-cell lymphoma^[12]
STAT5B	Src-like homologue 2 (SH2) domain of STAT5 Including: N642H mutation (associated with more aggressive disease)^[13]^[14] Causing constitutive phosphorylation of the mutated proteins, and increased the transcriptional activity of STAT5B in vitro^[10]^[11]	GOF	2%^[13]	Take caution as STAT5B mutations can also be seen in other T-cell lymphomas including hepatosplenic T-cell lymphoma^[12] N642H mutation is associated with CD3+/CD56+ phenotype^[14]
TNFAIP3	Somatic mutations^[9] Y353X K354K Q741Q E630X A717T F127C	LOF (Nonsense mutations)^[9]	Identified in 3/39 patients^[9]	In one study three of four of the patients with non‐synonymous TNFAIP3 alterations also harbored a STAT3 mutation (p = 0.004)^[9] TNFAIP3 itself is a NF‐κB target gene^[15]

*More comprehensive listing of specific mutations in these genes can be found elsewhere (COSMIC, cBioPortal)

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Epigenomic Alterations

Epigenetic inactivation of JAK/STAT pathway inhibitors
- SOCS3 has a crucial role in regulating STAT3 activation^[16]
- An epigenetic inhibition mechanism to SOCS3 gene is hypothesized^[16]
- KIR3DL1 has been shown to be down-modulated by hypermethylation of the promoter^[16]

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table. Do not delete table.)

Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
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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JAK/STAT^[7]
- Constitutive activation
NK-κB^[7]
- Activation of this pathway
- Preventing apoptosis
T-LGL's express high levels of FAS and FASL^[7]
- Resistant to FAS mediated apoptosis
- Leading to activation of prosurvival pathways
- Postulated to lead to neutropenia seen in these patients.
RAS/RAF1/MEK1/ERK ^[7]
- Overactive RAS
- Constitutive activation of RAS and ERK
PI3K/AKT^[7]
- Dysregulation
- Contributing to apoptosis inhibition

End of V4 Section

Genetic Diagnostic Testing Methods

Morphologic assessment, flow cytometry and immunohistochemistry
PCR to assess for clonality, T-cell receptor (TCR) gene rearrangements
- TCR gamma (TCRG) gene is rearranged in all cases, regardless of the type of TCR expressed, thus proves clonality^[1]
  - Can be helpful in differentiating a reactive lymphocytosis from clonal T-LGL's
- NK LGL proliferations do not express TCR, making assessment of clonality difficult^[7]
  - Expression of activating isoforms of killer immunoglobulin-like receptors (KIR) can be used as a surrogate marker of clonality in NK LGL^[7]

Familial Forms

No known familiar forms as of yet.

Additional Information

N/A

Links

Hepatosplenic T-cell lymphoma

References

(use the "Cite" icon at the top of the page) (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. 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.)

↑ ^{Jump up to: 1.0} ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 Chan W.C., et al., (2017). T-cell large granular lymphocytic leukemia, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p 348-350.
↑ Lima M, Almeida J, dos Anjos Teixeira M, del Carmen Alguero M, Santos AH, Balanzategui A, Queirós ML, Bárcena P, Izarra A, Fonseca S, Bueno C. TCRαβ+/CD4+ large granular lymphocytosis: a new clonal T-cell lymphoproliferative disorder. The American journal of pathology. 2003 Aug 1;163(2):763-71.
↑ Chen YH, Chadburn A, Evens AM, Winter JN, Gordon LI, Chenn A, Goolsby C, Peterson L. Clinical, morphologic, immunophenotypic, and molecular cytogenetic assessment of CD4–/CD8–γδ T-cell large granular lymphocytic leukemia. American journal of clinical pathology. 2011 Aug 1;136(2):289-99.
↑ ^{Jump up to: 4.0} ^4.1 Rajala HL, Olson T, Clemente MJ, Lagström S, Ellonen P, Lundan T, Hamm DE, Zaman SA, Marti JM, Andersson EI, Jerez A. The analysis of clonal diversity and therapy responses using STAT3 mutations as a molecular marker in large granular lymphocytic leukemia. haematologica. 2015 Jan 1;100(1):91-9.
↑ Loughran TP, Zickl L, Olson TL, Wang V, Zhang D, Rajala HL, Hasanali Z, Bennett JM, Lazarus HM, Litzow MR, Evens AM. Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998). Leukemia. 2015 Apr;29(4):886-94.
↑ Mishra A, Liu S, Sams GH, Curphey DP, Santhanam R, Rush LJ, Schaefer D, Falkenberg LG, Sullivan L, Jaroncyk L, Yang X. Aberrant overexpression of IL-15 initiates large granular lymphocyte leukemia through chromosomal instability and DNA hypermethylation. Cancer cell. 2012 Nov 13;22(5):645-55.
↑ ^{Jump up to: 7.0} ^7.1 ^7.2 ^7.3 ^7.4 ^7.5 ^7.6 ^7.7 Lamy T, Moignet A, Loughran TP. LGL leukemia: from pathogenesis to treatment. Blood. 2017 Mar 2;129(9):1082-94.
↑ ^{Jump up to: 8.0} ^8.1 Zhang L, Ramchandren R, Papenhausen P, Loughran TP, Sokol L. Transformed aggressive γδ‐variant T‐cell large granular lymphocytic leukemia with acquired copy neutral loss of heterozygosity at 17q11. 2q25. 3 and additional aberrations. European journal of haematology. 2014 Sep;93(3):260-4.
↑ ^{Jump up to: 9.0} ^9.1 ^9.2 ^9.3 ^9.4 ^9.5 Johansson P, Bergmann A, Rahmann S, Wohlers I, Scholtysik R, Przekopowitz M, Seifert M, Tschurtschenthaler G, Webersinke G, Jäger U, Siebert R. Recurrent alterations of TNFAIP 3 (A 20) in T‐cell large granular lymphocytic leukemia. International journal of cancer. 2016 Jan 1;138(1):121-4.
↑ ^{Jump up to: 10.0} ^10.1 Jerez A, Clemente MJ, Makishima H, Koskela H, LeBlanc F, Peng Ng K, Olson T, Przychodzen B, Afable M, Gomez-Segui I, Guinta K. STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia. Blood, The Journal of the American Society of Hematology. 2012 Oct 11;120(15):3048-57.
↑ ^{Jump up to: 11.0} ^11.1 ^11.2 Koskela HL, Eldfors S, Ellonen P, van Adrichem AJ, Kuusanmäki H, Andersson EI, Lagström S, Clemente MJ, Olson T, Jalkanen SE, Majumder MM. Somatic STAT3 mutations in large granular lymphocytic leukemia. New England Journal of Medicine. 2012 May 17;366(20):1905-13.
↑ ^{Jump up to: 12.0} ^12.1 Yabe M, Medeiros LJ, Wang SA, Tang G, Bueso-Ramos CE, Jorgensen JL, Bhagat G, Chen W, Li S, Young KH, Miranda RN. Distinguishing between hepatosplenic T-cell lymphoma and γδ T-cell large granular lymphocytic leukemia. The American journal of surgical pathology. 2017 Jan 1;41(1):82-93.
↑ ^{Jump up to: 13.0} ^13.1 Rajala HL, Eldfors S, Kuusanmäki H, Van Adrichem AJ, Olson T, Lagström S, Andersson EI, Jerez A, Clemente MJ, Yan Y, Zhang D. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood, The Journal of the American Society of Hematology. 2013 May 30;121(22):4541-50.
↑ ^{Jump up to: 14.0} ^14.1 Rajala HL, Porkka K, Maciejewski JP, Loughran Jr TP, Mustjoki S. Uncovering the pathogenesis of large granular lymphocytic leukemia—novel STAT3 and STAT5b mutations. Annals of Medicine. 2014 May 1;46(3):114-22.
↑ Zhang R, Shah MV, Yang J, Nyland SB, Liu X, Yun JK, Albert R, Loughran TP. Network model of survival signaling in large granular lymphocyte leukemia. Proceedings of the National Academy of Sciences. 2008 Oct 21;105(42):16308-13.
↑ ^{Jump up to: 16.0} ^16.1 ^16.2 Teramo, Antonella; et al. (2013-05-09). "Intrinsic and extrinsic mechanisms contribute to maintain the JAK/STAT pathway aberrantly activated in T-type large granular lymphocyte leukemia". Blood. 121 (19): 3843–3854, S1. doi:10.1182/blood-2012-07-441378. ISSN 1528-0020. PMID 23515927.

Notes

*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.

*Citation of this Page: “T-large granular lymphocytic leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 02/10/2025, https://ccga.io/index.php/HAEM5:T-large_granular_lymphocytic_leukaemia.

Other Sections

Cancer Category

Mature T- and NK-cell Neoplasm

[:0-1] {Jump up to: 1.0} ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 Chan W.C., et al., (2017). T-cell large granular lymphocytic leukemia, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p 348-350.

[2] Lima M, Almeida J, dos Anjos Teixeira M, del Carmen Alguero M, Santos AH, Balanzategui A, Queirós ML, Bárcena P, Izarra A, Fonseca S, Bueno C. TCRαβ+/CD4+ large granular lymphocytosis: a new clonal T-cell lymphoproliferative disorder. The American journal of pathology. 2003 Aug 1;163(2):763-71.

[3] Chen YH, Chadburn A, Evens AM, Winter JN, Gordon LI, Chenn A, Goolsby C, Peterson L. Clinical, morphologic, immunophenotypic, and molecular cytogenetic assessment of CD4–/CD8–γδ T-cell large granular lymphocytic leukemia. American journal of clinical pathology. 2011 Aug 1;136(2):289-99.

[:4-4] {Jump up to: 4.0} ^4.1 Rajala HL, Olson T, Clemente MJ, Lagström S, Ellonen P, Lundan T, Hamm DE, Zaman SA, Marti JM, Andersson EI, Jerez A. The analysis of clonal diversity and therapy responses using STAT3 mutations as a molecular marker in large granular lymphocytic leukemia. haematologica. 2015 Jan 1;100(1):91-9.

[5] Loughran TP, Zickl L, Olson TL, Wang V, Zhang D, Rajala HL, Hasanali Z, Bennett JM, Lazarus HM, Litzow MR, Evens AM. Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998). Leukemia. 2015 Apr;29(4):886-94.

[6] Mishra A, Liu S, Sams GH, Curphey DP, Santhanam R, Rush LJ, Schaefer D, Falkenberg LG, Sullivan L, Jaroncyk L, Yang X. Aberrant overexpression of IL-15 initiates large granular lymphocyte leukemia through chromosomal instability and DNA hypermethylation. Cancer cell. 2012 Nov 13;22(5):645-55.

[:9-7] {Jump up to: 7.0} ^7.1 ^7.2 ^7.3 ^7.4 ^7.5 ^7.6 ^7.7 Lamy T, Moignet A, Loughran TP. LGL leukemia: from pathogenesis to treatment. Blood. 2017 Mar 2;129(9):1082-94.

[:3-8] {Jump up to: 8.0} ^8.1 Zhang L, Ramchandren R, Papenhausen P, Loughran TP, Sokol L. Transformed aggressive γδ‐variant T‐cell large granular lymphocytic leukemia with acquired copy neutral loss of heterozygosity at 17q11. 2q25. 3 and additional aberrations. European journal of haematology. 2014 Sep;93(3):260-4.

[:6-9] {Jump up to: 9.0} ^9.1 ^9.2 ^9.3 ^9.4 ^9.5 Johansson P, Bergmann A, Rahmann S, Wohlers I, Scholtysik R, Przekopowitz M, Seifert M, Tschurtschenthaler G, Webersinke G, Jäger U, Siebert R. Recurrent alterations of TNFAIP 3 (A 20) in T‐cell large granular lymphocytic leukemia. International journal of cancer. 2016 Jan 1;138(1):121-4.

[:1-10] {Jump up to: 10.0} ^10.1 Jerez A, Clemente MJ, Makishima H, Koskela H, LeBlanc F, Peng Ng K, Olson T, Przychodzen B, Afable M, Gomez-Segui I, Guinta K. STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia. Blood, The Journal of the American Society of Hematology. 2012 Oct 11;120(15):3048-57.

[:2-11] {Jump up to: 11.0} ^11.1 ^11.2 Koskela HL, Eldfors S, Ellonen P, van Adrichem AJ, Kuusanmäki H, Andersson EI, Lagström S, Clemente MJ, Olson T, Jalkanen SE, Majumder MM. Somatic STAT3 mutations in large granular lymphocytic leukemia. New England Journal of Medicine. 2012 May 17;366(20):1905-13.

[:5-12] {Jump up to: 12.0} ^12.1 Yabe M, Medeiros LJ, Wang SA, Tang G, Bueso-Ramos CE, Jorgensen JL, Bhagat G, Chen W, Li S, Young KH, Miranda RN. Distinguishing between hepatosplenic T-cell lymphoma and γδ T-cell large granular lymphocytic leukemia. The American journal of surgical pathology. 2017 Jan 1;41(1):82-93.

[:7-13] {Jump up to: 13.0} ^13.1 Rajala HL, Eldfors S, Kuusanmäki H, Van Adrichem AJ, Olson T, Lagström S, Andersson EI, Jerez A, Clemente MJ, Yan Y, Zhang D. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood, The Journal of the American Society of Hematology. 2013 May 30;121(22):4541-50.

[:8-14] {Jump up to: 14.0} ^14.1 Rajala HL, Porkka K, Maciejewski JP, Loughran Jr TP, Mustjoki S. Uncovering the pathogenesis of large granular lymphocytic leukemia—novel STAT3 and STAT5b mutations. Annals of Medicine. 2014 May 1;46(3):114-22.

[15] Zhang R, Shah MV, Yang J, Nyland SB, Liu X, Yun JK, Albert R, Loughran TP. Network model of survival signaling in large granular lymphocyte leukemia. Proceedings of the National Academy of Sciences. 2008 Oct 21;105(42):16308-13.

[:10-16] {Jump up to: 16.0} ^16.1 ^16.2 Teramo, Antonella; et al. (2013-05-09). "Intrinsic and extrinsic mechanisms contribute to maintain the JAK/STAT pathway aberrantly activated in T-type large granular lymphocyte leukemia". Blood. 121 (19): 3843–3854, S1. doi:10.1182/blood-2012-07-441378. ISSN 1528-0020. PMID 23515927.

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+<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.}}</blockquote><ref name=":0">Chan W.C., et al., (2017). T-cell large granular lymphocytic leukemia, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p 348-350.</ref><blockquote class="blockedit">
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+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+</blockquote>
 </blockquote>
 ==Sites of Involvement==
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+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+</blockquote>
 ==Morphologic Features==
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+<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.}}</blockquote><ref name=":0" /><blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+</blockquote>
 ==Chromosomal Rearrangements (Gene Fusions)==
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 *No known chromosomal rearrangements
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
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 * Individual Region Genomic Gain/Loss/LOH
 * Characteristic Chromosomal Patterns
-* Gene Mutations (SNV/INDEL)}}
+* Gene Mutations (SNV/INDEL)}}</blockquote>
 *There are no FDA approved targeted therapies for T-LGL
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 *Bortezomib is considered due to NF-κB  constitutive activity in T-LGL leukemia<ref>Mishra A, Liu S, Sams GH, Curphey DP, Santhanam R, Rush LJ, Schaefer D, Falkenberg LG, Sullivan L, Jaroncyk L, Yang X. Aberrant overexpression of IL-15 initiates large granular lymphocyte leukemia through chromosomal instability and DNA hypermethylation. Cancer cell. 2012 Nov 13;22(5):645-55.</ref>
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
 ==Individual Region Genomic Gain / Loss / LOH==
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 |}
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 *No known recurrent copy number gain/loss/LOH, chromosomal abnormalities have been reported in few cases<ref name=":9" />
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
 ==Characteristic Chromosomal Patterns==
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 *No characteristic chromosomal aberrations have been identified
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 ***
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+----
 </blockquote>
 ==Gene Mutations (SNV / INDEL)==
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 Somatic activating STAT3 and STAT5b mutations are the most common SNVs in T-LGL.
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 <nowiki>*</nowiki>More comprehensive listing of specific mutations in these genes can be found elsewhere ([https://cancer.sanger.ac.uk/cosmic COSMIC], [https://www.cbioportal.org/ cBioPortal])
 <br />
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+----
 </blockquote>
 ==Epigenomic Alterations==
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 |}
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 *JAK/STAT<ref name=":9" />
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 **Contributing to apoptosis inhibition
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
 ==Genetic Diagnostic Testing Methods==

Difference between revisions of "HAEM5:T-large granular lymphocytic leukaemia"

Revision as of 13:33, 10 February 2025

Primary Author(s)*

Contents

WHO Classification of Disease

Definition / Description of Disease

Synonyms / Terminology

Epidemiology / Prevalence

Clinical Features

Sites of Involvement

Morphologic Features

Immunophenotype

Chromosomal Rearrangements (Gene Fusions)

Individual Region Genomic Gain / Loss / LOH

Characteristic Chromosomal Patterns

Gene Mutations (SNV / INDEL)

Epigenomic Alterations

Genes and Main Pathways Involved

Genetic Diagnostic Testing Methods

Familial Forms

Additional Information

Links

References

Notes

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