scholarly journals Humoral immune failure defined by immunoglobulin class and immunoglobulin G subclass deficiency is associated with shorter treatment‐free and overall survival in Chronic Lymphocytic Leukaemia

2018 ◽  
Vol 181 (1) ◽  
pp. 97-101 ◽  
Author(s):  
Kyle R. Crassini ◽  
Eva Zhang ◽  
Shalini Balendran ◽  
Jane A. Freeman ◽  
O. Giles Best ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukaemia ◽  
Immunoglobulin G ◽  
Lymphocytic Leukaemia ◽  
Immunoglobulin Class ◽  
Humoral Immune ◽  
Subclass Deficiency ◽  
Immunoglobulin G Subclass ◽  
Immune Failure

Multicentre validation of a prognostic index for overall survival in chronic lymphocytic leukaemia

2010 ◽  
Vol 29 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Pietro Bulian ◽  
Michela Tarnani ◽  
Davide Rossi ◽  
Francesco Forconi ◽  
Giovanni Del Poeta ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Prognostic Index

Chronic Lymphocytic Leukaemia Has a More Aggressive Phenotype in Asians Compared to Caucasians.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4965-4965
Author(s):  
Belinda Austen ◽  
Chaminda Gunawardana ◽  
Guy Pratt ◽  
Farooq Wandroo ◽  
Abe Jacobs ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Age Of Onset ◽  
Western World ◽  
Control Group ◽  
Aggressive Phenotype ◽  
Racial Origin ◽  
Asian Patients ◽  
Younger Age

Abstract Chronic lymphocytic leukaemia (CLL) is the commonest leukaemia in the western world with an incidence of 3 per 100,000. The precise aetiology remains obscure but there is clear evidence for a genetic predisposition. CLL has a seven-fold increased incidence amongst relatives of index cases compared to controls and the disease is also more common in males. These genetic subgroups can also determine phenotype as familial CLL has a younger age of onset and increased association with second malignancies compared to sporadic cases. Similarly, CLL is more aggressive and more frequently requires treatment in males in comparison to female patients. The incidence of CLL also varies according to racial origin and has been found to be up to 20-fold less common in Japanese and Asian populations compared to Caucasian populations. However, it is not known whether or not there is also phenotypic variation in CLL patients according to racial origin. We studied 29 Asian patients with a diagnosis of CLL and compared disease characteristics with a control group of 277 Caucasians. We found that CLL in Asians was diagnosed at a younger age (median age 62yr in Asians vs 70yr Caucasians, p=0.001) and was also more common in males (M:F Asians 3.1:1; Caucasians 1.3:1, p=0.023). No association was seen between racial origin and either IGVH status or CD38 status. Interestingly, we also found that the Asian population had a more aggressive clinical phenotype as indicated by a shorter time to the requirement of first treatment (TTFT) (p=0.019). This observation was independent of both age and gender. Although no difference was seen in overall survival between the two groups, ‘non-leukaemia related’ deaths were more common in the older Caucasian population. 27.5% of Caucasian deaths occurred in patients who had never required treatment for CLL whereas no deaths occurred among untreated Asian patients, for whom the primary cause of death was progressive leukaemia. The failure to observe a difference in overall survival was therefore partly accounted for by an increase in non-leukaemia related deaths in Caucasians. In conclusion, we have shown that there are phenotypic differences in CLL patients according to the racial origin. CLL in Asian patients occurs at a younger age and is associated with a more aggressive phenotype. The mechanisms underlying these observations are unknown but warrant further investigation.

Levels of Phosphorylated P70 S6 Kinase and Phosphorylated ERK1&2 Predict Overall Survival and Time to First Treatment In Chronic Lymphocytic Leukaemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1363-1363
Author(s):  
James R Bailey ◽  
Gina L Eagle ◽  
Pointon Jo ◽  
Ria Brathwaite ◽  
Abbott Jody ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Overall Survival ◽  
Chronic Lymphocytic Leukaemia ◽  
B Cell ◽  
Median Time ◽  
Lymphocytic Leukaemia ◽  
S6 Kinase ◽  
P70 S6 Kinase ◽  
Time To First Treatment ◽  
Extracellular Regulated Kinase

Abstract Abstract 1363 Chronic lymphocytic leukaemia (CLL) is a clinically heterogeneous disease characterised by an accumulation of malignant B lymphocytes. Central to the survival of CLL-cells is the B-cell Receptor (BCR), a structurally complex moiety which contains an immunoglobulin molecule with antigenic specificity. Stimulation of the BCR by antigen binding may lead to the activation of multiple intracellular kinase cascades with a variety of intracellular functions. Kinases known to be activated include phosphorylated Extracellular Regulated Kinase (pERK) and P70 S6 Kinase (P70S6K). Increased levels of phosphorylated Extracellular Regulated Kinase (pERK) are found in CLL cells induced to proliferate and inhibition of the ERK pathway promotes chemotherapy induced apoptosis in B-cell lines. P70S6K regulates cell cycle behaviour in B cells and it has been shown that inhibition of P70S6K activation by phosphorylation with rapamycin leads to cell cycle arrest in CLL cells. We investigated the relationships between pERK isoforms 1&2 (pERK1&2) and phosphorylated-P70S6K concentrations (both baseline and after BCR-crosslinking) and overall survival (OS) as well as time to first treatment (TTFT) in a cohort of patients with CLL. Lymphocytes were isolated from patients with CLL attending Haematology Clinic at the Hull and East Yorkshire NHS Trust. Collections were made after taking informed consent according to the Declaration of Helsinki with Local Ethics Committee approval (05/Q1104/33). pERK1&2 concentrations and phospho-P70S6K were measured quantitatively using ELISA according to the manufacturer's protocol (#SUV1018 &#DYC896, RnD Systems) in 99 such cases. Kinase concentrations were assayed at baseline in unstimulated cells and also after stimulation by antibody mediated BCR-crosslinking using a goat anti-human IgM antibody (#109-006-129, Jackson ImmunoResearch). The mutational status of the variable region of the immunoglobulin gene (IgVH status) was determined in all cases. The pERK1&2 and phospho-P70S6K concentrations measured were correlated with clinical stage, IgVH, ZAP70 and CD38 status. The individual kinase concentration measurements were then ranked and those in the upper quartile were regarded as being elevated. Statistical analysis was performed to assess the relationships between elevated pERK1&2 and phospho-P70S6K concentrations and OS/TTFT in both unstimulated CLL cells as well as after BCR-crosslinking. An elevated baseline concentration of intracellular pERK1&2 was found to define a subset of IgVH mutated patients with a reduced mean overall survival (157 vs. 259 months, p=0.011) and, also, to identify patients with a shorter median time to first treatment (8 vs. 31 months, p=0.050). An elevated baseline concentration of P70S6K defined subsets of both IgVH mutated (168 vs. 254 months, p=0.046) and CD38 positive (57 vs. 234 months, p=0.000) patients with a reduced overall survival. An elevated concentration of pERK after BCR-crosslinking was shown to define a subset of ZAP70 negative patients with reduced overall survival (99 vs. 233 months, p=0.020), as well as identifying patients with a shorter median time to first treatment (8 vs. 37 months, p=0.011). Our results demonstrate that increased baseline intracellular pERK1&2 and phospho-P70S6K concentrations can be used in conjunction with established prognostic markers to identify patients with a reduced OS and, in the case of pERK1&2, TTFT. An unmutated IgVH status was associated with higher absolute pERK1&2 and phospho-P70S6K baseline concentrations. This suggests that increased intracellular signalling activity may contribute to the adverse prognosis seen in unmutated IgVH patients. The findings support the investigation of kinase inhibitors as novel agents in the management of bad risk CLL. Disclosures: No relevant conflicts of interest to declare.

Kartagener's syndrome with immunoglobulin G subclass deficiency

2013 ◽  
Vol 1 (3) ◽  
pp. 288 ◽  
Author(s):  
Ki-Chan Kim ◽  
Joo-Han Park ◽  
Ga-Young Ban ◽  
Hye-Soo Yoo ◽  
Yoo-Seob Shin ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Kartagener's Syndrome ◽  
Subclass Deficiency ◽  
Immunoglobulin G Subclass

The Challenge of Immunoglobulin-G Subclass Deficiency and Specific Polysaccharide Antibody Deficiency – a Dutch Pediatric Cohort Study

2016 ◽  
Vol 36 (2) ◽  
pp. 141-148 ◽  
Author(s):  
Ellen J. H. Schatorjé ◽  
Everieke de Jong ◽  
Roeland W. N. M. van Hout ◽  
Yumely García Vivas ◽  
Esther de Vries
Keyword(s):  
Cohort Study ◽  
Immunoglobulin G ◽  
Antibody Deficiency ◽  
Specific Polysaccharide ◽  
Subclass Deficiency ◽  
Polysaccharide Antibody ◽  
Immunoglobulin G Subclass

scholarly journals Nasal polyposis and immunoglobulin-G subclass deficiency

2014 ◽  
Vol 131 (3) ◽  
pp. 171-175 ◽  
Author(s):  
N. Tran Khai Hoan ◽  
M. Karmochkine ◽  
O. Laccourreye ◽  
P. Bonfils
Keyword(s):  
Immunoglobulin G ◽  
Nasal Polyposis ◽  
Subclass Deficiency ◽  
Immunoglobulin G Subclass
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