HOT TOPICS Flashcards
(20 cards)
What is LGL leukemia?
A rare lymphoproliferative disorder characterized by an expansion of clonal T or natural killer lymphocytes
LGL stands for large granular lymphocyte, and this condition is often associated with autoimmune disorders.
What are the main manifestations of LGL leukemia?
Neutropenia-related infections and anemia
These manifestations arise due to the expansion of lymphocytes affecting normal blood cell production.
What autoimmune disorders are frequently associated with LGL leukemia?
- Rheumatoid arthritis
- Sjögren’s syndrome
- Autoimmune endocrinopathies
- Vasculitis
- Autoimmune cytopenia
The association highlights the interplay between immune dysregulation and malignancy.
What is the role of the Jak/STAT signaling pathway in LGL leukemia?
It is dysregulated, linking leukemic-cell expansion and autoimmunity
Chronic antigenic stimulation is also pivotal in the pathophysiology of the disease.
What percentage of LGL leukemia patients have a somatic STAT3 mutation?
More than half of patients
This mutation is crucial for the disease’s pathogenesis.
What is the first-line treatment for LGL leukemia?
Immunosuppressive agents such as methotrexate, cyclophosphamide, or cyclosporine
New approaches are being explored, including cytokine blocking molecules or Jak/STAT inhibitors.
What are the mandatory criteria for diagnosing LGL leukemia?
- Elevated number of circulating LGL cells (>0.5 × 10^9 /L)
- Proof of clonality obtained by flow cytometry and/or molecular biology
These criteria help distinguish LGL leukemia from reactive LGL expansion.
How are large granular lymphocytes (LGLs) characterized morphologically?
Large cells (15-20 µm) with abundant cytoplasm containing azurophilic granules and a reniform or round nucleus with mature chromatin
LGLs normally represent 10%-15% of mononuclear cells.
What is the T-cell phenotype of LGL leukemia in most cases?
CD3+ T-cell phenotype (85% of diagnoses)
The remaining cases are predominantly NK-LGL with a CD3− CD56+/CD16+ phenotype.
What method is the gold standard for demonstrating clonal rearrangement in T-LGL leukemia?
Polymerase chain reaction using primers targeting the conserved region of the VDJ segments
This method provides definitive evidence of clonality.
What are the common subtypes of T-LGL leukemias?
- CD3+ αβ+ CD8+ CD57+ (80%)
- CD3+ γδ+ CD4− CD8− (15%)
- CD3+ αβ+ CD4+ CD8+ (5%)
These subtypes exhibit distinct phenotypic characteristics.
What is the hallmark mutation of LGL leukemia identified in 2001?
Constitutive activation of STAT3
This mutation affects key T-cell functions and is critical in the disease’s pathogenesis.
What percentage of T-LGL patients have STAT3 gain-of-function mutations?
Up to 60%
This mutation increases transcription of antiapoptotic and proinflammatory genes.
What autoimmune disorder is most commonly associated with LGL leukemia?
Rheumatoid arthritis (RA)
RA affects 10%-15% of patients with LGL leukemia.
What is the connection between RA and LGL leukemia?
Activation of the Jak/STAT pathway and inflammatory cytokines are implicated in both diseases
Patients with both conditions share a similar proinflammatory cytokine profile.
What is the significance of the HLA-DR4 phenotype in LGL leukemia and RA?
In 90% of cases with both diseases, patients display the HLA-DR4 phenotype
This is significantly higher compared to RA patients without LGL leukemia.
What are the implications of IFN-γ response genes in nonleukemic immune cells?
They are upregulated and may support leukemic T-LGL growth
This suggests a complex interaction between leukemic and nonleukemic immune cells.
What percentage of NK-LGL patients have CCL22 gene mutations?
27%
These mutations are mutually exclusive of STAT3 mutations and affect cellular chemotaxis.
What is the relationship between autoimmune manifestations and the treatment of LGL leukemia?
Regression of autoimmune manifestations often follows the treatment of LGL leukemia
This indicates a potential causal relationship between the two conditions.
What is the debate surrounding the relationship between autoimmune disorders and LGL leukemia?
Whether autoimmune disorders are a cause or a consequence of LGL leukemia
This is compared to the ‘chicken or the egg’ conundrum.
