HAEM5:T-large granular lymphocytic leukaemia: Difference between revisions
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**An epigenetic inhibition mechanism to SOCS3 gene is hypothesized<ref name=":10" /> | **An epigenetic inhibition mechanism to SOCS3 gene is hypothesized<ref name=":10" /> | ||
**KIR3DL1 has been shown to be down-modulated by hypermethylation of the promoter<ref name=":10" /> | **KIR3DL1 has been shown to be down-modulated by hypermethylation of the promoter<ref name=":10" /> | ||
**Mutations in KMT2D and TET2 have been found to significantly co-occur with STAT3 mutations< | **Mutations in KMT2D and TET2 have been found to significantly co-occur with STAT3 mutations<ref name=":0" /> | ||
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==Genes and Main Pathways Involved== | ==Genes and Main Pathways Involved== | ||
<span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span> | |||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome | !Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome | ||
|- | |- | ||
|JAK/STAT< | |JAK/STAT<ref name=":3" /> | ||
|Constitutive activation | |Constitutive activation | ||
|Dysregulation of apoptosis | |Dysregulation of apoptosis | ||
|- | |- | ||
|NK-kB< | |NK-kB<ref name=":3" /> | ||
|Pathway activation | |Pathway activation | ||
|Preventing apoptosis | |Preventing apoptosis | ||
|- | |- | ||
|FAS and FASL< | |FAS and FASL<ref name=":3" /> | ||
|Resistance to FAS mediated apoptosis | |Resistance to FAS mediated apoptosis | ||
|Activation of pro-survival pathways which is postulated to lead to neutropenia | |Activation of pro-survival pathways which is postulated to lead to neutropenia | ||
|- | |- | ||
|RAS/RAF1/MEK1/ERK< | |RAS/RAF1/MEK1/ERK<ref name=":3" /> | ||
|Overactive RAS | |Overactive RAS | ||
|Constitutive activation of RAS and ERK | |Constitutive activation of RAS and ERK | ||
|- | |- | ||
|PI3K/AKT< | |PI3K/AKT<ref name=":3" /> | ||
|Dysregulation | |Dysregulation | ||
|Apoptosis inhibition | |Apoptosis inhibition | ||
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*Morphologic assessment, flow cytometry and immunohistochemistry | *Morphologic assessment, flow cytometry and immunohistochemistry | ||
*PCR to assess for clonality, T-cell receptor (TCR) gene rearrangements | *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 | ** TCR gamma (TCRG) gene is rearranged in all cases, regardless of the type of TCR expressed, thus proves clonality<ref name=":9" /> | ||
** Can be helpful in differentiating a reactive lymphocytosis from clonal T-LGL's | ** 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 | *** NK LGL proliferations do not express TCR, making assessment of clonality difficult<ref name=":3" /> | ||
*** Expression of activating isoforms of killer immunoglobulin-like receptors (KIR) can be used as a surrogate marker of clonality in NK LGL | *** Expression of activating isoforms of killer immunoglobulin-like receptors (KIR) can be used as a surrogate marker of clonality in NK LGL<ref name=":3" /> | ||
* Myeloid neoplasms may present with clonal large granular lymphocyte expansion with STAT3/STAT5B mutations. Next generation sequencing can be diagnostically useful in these cases< | * Myeloid neoplasms may present with clonal large granular lymphocyte expansion with STAT3/STAT5B mutations. Next generation sequencing can be diagnostically useful in these cases<ref>{{Cite journal|last=Kavesh|first=Mark|last2=Mohebnasab|first2=Maedeh|last3=Angel|first3=Marcela Riveros|last4=Xie|first4=Wei|last5=Raess|first5=Philipp W.|last6=Cui|first6=Wei|last7=Press|first7=Richard D.|last8=Yang|first8=Guang|last9=Li|first9=Peng|date=2023-01-10|title=Distinguishing STAT3/STAT5B -mutated large granular lymphocyte leukemia from myeloid neoplasms by genetic profiling|url=https://ashpublications.org/bloodadvances/article/7/1/40/486140/Distinguishing-STAT3-STAT5B-mutated-large-granular|journal=Blood Advances|language=en|volume=7|issue=1|pages=40–45|doi=10.1182/bloodadvances.2022008192|issn=2473-9529}}</ref> | ||
==Familial Forms== | ==Familial Forms== | ||
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==Additional Information== | ==Additional Information== | ||
*PI3K-Akt has been found to be upregulated in KLRG1<sup>-</sup> CD8<sup>+</sup> T-LGLL. Studies are being conducted to examine treatment with linperlisib.< | *PI3K-Akt has been found to be upregulated in KLRG1<sup>-</sup> CD8<sup>+</sup> T-LGLL. Studies are being conducted to examine treatment with linperlisib.<ref>{{Cite journal|last=Zhang|first=Lele|last2=Qiu|first2=Chen|last3=Li|first3=Ruonan|last4=Shen|first4=Yucan|last5=Tian|first5=Linzhu|last6=Chang|first6=Hong|last7=Liang|first7=Qian|last8=Pan|first8=Hong|last9=Gao|first9=Zhen|date=2025-04|title=KLRG1 re-defines a leukemic clone of CD8 effector T cells sensitive to PI3K inhibitor in T cell large granular lymphocytic leukemia|url=https://linkinghub.elsevier.com/retrieve/pii/S2666379125001090|journal=Cell Reports Medicine|language=en|volume=6|issue=4|pages=102036|doi=10.1016/j.xcrm.2025.102036|pmc=12047471|pmid=40147444}}</ref> | ||
*Myleoid clonal hematopoiesis is associated with the presence of cytopenia in LGLL< | *Myleoid clonal hematopoiesis is associated with the presence of cytopenia in LGLL<ref name=":1" /> | ||
==Links== | ==Links== | ||