HAEM5:T-large granular lymphocytic leukaemia: Difference between revisions
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{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Chr #!! | !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 | ||
|- | |- | ||
|<span class="blue-text">EXAMPLE:</span> | |<span class="blue-text">EXAMPLE:</span> | ||
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!Chromosomal Pattern | !Chromosomal Pattern | ||
!Molecular Pathogenesis | !Molecular Pathogenesis | ||
! | !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 | ||
|- | |- | ||
|<span class="blue-text">EXAMPLE:</span> | |<span class="blue-text">EXAMPLE:</span> | ||
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{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Gene!! | !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 | ||
|- | |- | ||
|<span class="blue-text">EXAMPLE:</span>''EGFR'' | |<span class="blue-text">EXAMPLE:</span>''EGFR'' | ||
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*Causing constitutive phosphorylation of the mutated proteins, and increased the transcriptional activity of STAT3 in vitro<ref name=":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.</ref><ref name=":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.</ref> | *Causing constitutive phosphorylation of the mutated proteins, and increased the transcriptional activity of STAT3 in vitro<ref name=":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.</ref><ref name=":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.</ref> | ||
| | |GOF||40-70%<ref name=":2" /> | ||
| | | | ||
*17% of patients with STAT3 mutations, had multiple mutations in the STAT3 gene, solely in cytotoxic CD8+ or NK cells.<ref name=":4">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.</ref> | *17% of patients with STAT3 mutations, had multiple mutations in the STAT3 gene, solely in cytotoxic CD8+ or NK cells.<ref name=":4">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.</ref> | ||
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*Causing constitutive phosphorylation of the mutated proteins, and increased the transcriptional activity of STAT5B in vitro<ref name=":1" /><ref name=":2" /> | *Causing constitutive phosphorylation of the mutated proteins, and increased the transcriptional activity of STAT5B in vitro<ref name=":1" /><ref name=":2" /> | ||
* | * | ||
| | |GOF | ||
|2%<ref name=":7">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.</ref> | |2%<ref name=":7">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.</ref> | ||
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**A717T | **A717T | ||
**F127C | **F127C | ||
| | |LOF (Nonsense mutations)<ref name=":6" /> | ||
|Identified in 3/39 patients<ref name=":6" /> | |Identified in 3/39 patients<ref name=":6" /> | ||
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