Genetic susceptibility to chronic lymphocytic leukemia

Houlston, Richard S.; Catovsky, Daniel; Yuille, Martin

doi:10.1038/sj.leu.2402538

Cited by 40 publications

(28 citation statements)

References 58 publications

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“…inherited genetic predispositions to cll has directed attention towards extensive studies on genetic alterations which could disturb gene expression (6,32). Studies looking for new genetic aberrations and epigenetic modifications in chromatin structure have been performed (4)(5)(6).…”

Section: Discussionmentioning

confidence: 99%

Relationship between in vitro drug sensitivity and clinical response of patients to treatment in chronic lymphocytic leukemia

Rogalińska

Błoński

Góralski

et al. 2015

International Journal of Oncology

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Abstract. to improve the efficacy of therapeutic options in chronic lymphocytic leukemia (cll) an in vitro system to determine the response of mononuclear blood cells from blood of patients was elaborated. the study combines four approaches, i.e., cell viability, apoptosis rate, differential scanning calorimetry (DSc), and immunoblotting to develop personalized therapy protocols based on the cell sensitivity to drug exposure of individual cll patients. the complementary analyses were performed on 28 peripheral blood samples from previously untreated cll patients before therapy. the induction and progress of apoptosis in cll cells exposed in vitro to purine analogs combined with mafosfamide, i.e., cladribine + mafosfamide (CM) and fludarabine + mafosfamide (fM) were assessed using the above approaches. the changes in thermal profiles (decrease/loss of transition at 95±5˚C) coincided with an accumulation of apoptotic cells, a decrease in the number of viable cells, and differences in the expression of the apoptosis-related protein ParP-1. no significant changes were observed in the thermal profiles of nuclei isolated from cll cells resistant to the treatment. the complementary assays revealed a strong relationship between both the in vitro sensitivity of leukemia cells to drugs and the clinical response of the patients, determined usually after the sixth course of treatment (after ~6 months of therapy). as a summary of studies followed by complementary tests, our findings demonstrate the value of in vitro exposure of cll cell samples to drugs intended to treat cll patients, before their administration in order to recommend the most suitable and effective therapy for individual patients.

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Section: Discussionmentioning

confidence: 99%

Relationship between in vitro drug sensitivity and clinical response of patients to treatment in chronic lymphocytic leukemia

Rogalińska

Błoński

Góralski

et al. 2015

International Journal of Oncology

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“…The etiology of B-CLL, however, is not well understood. Interestingly, a number of observations including significant familial aggregation of B-CLL cases as well as racial differences in its incidence suggest that inherited background plays an important role in B-CLL development (2).…”

Section: Introductionmentioning

confidence: 99%

CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians

Jamroziak¹,

Szemraj²,

Grzybowska–Izydorczyk³

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Given the recent findings on the importance of CD38 signaling in the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL), we hypothesized that single nucleotide polymorphisms (SNP) in the CD38 gene may be related to B-CLL risk. We evaluated two potentially functional CD38 SNPs, intronic rs6449182 (184C>G) and missense rs1800561 (418C>T, Arg 140 Trp) in two hospitalbased case-control studies (study A and validation study B). Genotyping was done using PCR-based assays in a total of 460 Polish Caucasian patients with B-CLL and 503 age-matched and gender-matched controls. We found that frequencies of both variant alleles (rs6449182 G and rs1800561 T) were significantly higher in B-CLL. In study A, logistic regression analysis revealed an association between B-CLL and genotypes: rs6449182 CG [odds ratio (OR), 3.57; 95% confidence interval (95% CI), 2.4-5.3], rs6449182 GG (OR, 5.2; 95% CI, 2.36-11.5), and rs1800561 CT (OR, 6.72; 95% CI, 1.5-30.1), although no homozygous rs1800561 TT genotype was detected in either study. These results were confirmed in study B, which showed an association between B-CLL and genotypes rs6449182 CG (OR, 4.00; 95% CI, 2.7-6.0), rs6449182 GG (OR, 12.84; 95% CI, 4.3-38.7), and rs1800561 CT (OR, 10.12; 95% CI, 1.3-81.6), and in the combined analysis of both studies. We also observed that rs6449182 G carriers had more advanced clinical stage (P = 0.002) and tended to be younger at diagnosis (P = 0.056). Furthermore, we found higher CD38 transcript levels and higher proportions of CD38-positive cells in carriers of rs6449182 G and rs1800561 T alleles (P < 0.05 for all comparisons). In conclusion, our data show that CD38 SNPs may affect CD38 expression and contribute to the increased risk of B-CLL carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2009;18(3):945 -53)

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“…[3][4][5] Furthermore anticipation phenomenon is reported in some familial cases. 6 These studies suggest that CLL has an important genetic basis.…”

mentioning

confidence: 99%

Association of TGF-1 Gene (+915G>C) Polymorphism with Chronic Lymphocytic Leukemia

Yunus¹,

Yılmaz²,

Çebi³

et al. 2015

UHOD

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TGFβ1 is an important cytokine acts as an antiinflammatory agent, and inhibits B cell proliferation. In patients with chronic lymphocytic leukemia (CLL), serum level of TGFβ1 are found elevated. Presence of G allele at position +915 in TGFβ1 gene results in arginine synthesis which is associated with higher expression of TGFβ1. We investigated the association of TGFβ1 +915G>C polymorphism with predisposition, clinical characteristics and laboratory findings of CLL. 50 CLL patients and 50 healthy controls were included in this study. Genotypes were determined by PCR-RFLP method. We couldn't find statistically significant differences between patient and control groups in terms of genotype distributions and allele frequencies. However, GC genotype frequency was slightly higher in CLL patients than healthy controls. hastalarında ilginç olarak TGFβ1 serum seviyeleri artmış olarak saptanmıştır. TGFβ1 (+915G>C) polimorfizminde Arjinin aminoasidi ile ilişkili olan G alleli varlığında TGFβ1 ekspresyonu artmış olarak saptanmaktadır. Bu çalışmada TGFβ1 (+915G>C) polimorfizminin KLL hastalığına yatkınlık, klinik özellikler ve laboratuar bulguları ile ilişkisi incelenmiştir. Çalışmaya KLL tanısı almış 50 hasta birey ve sağlıklı kontrol grubu olarak 50 gönüllü birey dahil edilmiştir. TGFβ1 (+915G>C) genotipleri PCR-RFLP metodu ile belirlenmiştir. Çalışma sonucunda hasta grup ile sağlıklı kontrol grubu arasında genotip dağılımı ve allel frekansı açısından anlamlı bir fark saptanmamıştır. Bununla birlikte KLL hastalarında GC genotipi, istatistiksel olarak anlamlı olmasa da, kontrol grubuna göre daha fazla görülmüştür. Ayrıca TGFβ1 +915GC genotipi ile trizomi 12 varlığı arasında anlamlı bir ilişki saptanmıştır (p= 0.007). TGFβ1 +915G>C polimorfizmi ile trizomi 12 ve KLL arasındaki ilişkiyi açıklamak için başka çalışmalara da ihtiyaç vardır.

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Genetic susceptibility to chronic lymphocytic leukemia

Abstract: There is increasing evidence that a subset of chronic lymphocytic leukemia is caused by an inherited predisposition. Here we review the evidence for an inherited predisposition, the characteristics of familial cases and evidence for the involvement of specific genes.

Cited by 40 publications

References 58 publications

Relationship between in vitro drug sensitivity and clinical response of patients to treatment in chronic lymphocytic leukemia

Relationship between in vitro drug sensitivity and clinical response of patients to treatment in chronic lymphocytic leukemia

CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians

Association of TGF-1 Gene (+915G>C) Polymorphism with Chronic Lymphocytic Leukemia

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