HLA allele repertoire in Russian chronic lymphocytic leukemia patients with an unfavorable prognosis

Introduction. An unfavorable prognosis in chronic lymphocytic leukemia (CLL) is associated with unmutated status of rearranged IGHV genes. CLL is also characterized by a narrowing of the repertoire of IGHV genes and the formation of quasiidentical (stereotyped) receptors, which is probably associated with antigenic selection of the tumor B-cell clone in the pathogenesis of the disease. The HLA phenotype plays an important role in antigenic selection of B cells. On the other hand, the association of specifi c HLA alleles with various diseases has been described. Aim. To assess the frequencies of HLA alleles in CLL patients with unmutated IGHV genes and the most common stereotyped receptors (SARs). Materials and methods. The study included 100 CLL patients with unmutated IGHV genes - 50 with the most common stereotyped antigen receptors (SARs) and 50 with non-stereotyped antigenic receptors. Control group of healthy donors was also included. Results. Signifi cant differences in HLA-allele repertoire between this two groups of patients and groups of donors were found. B*18 allele group was found much more common in patients with SARs than in donors and in patients without SARs. HLA-B*39 was more frequent for patients with SARs compared to donors; in patients without SARs these alleles were not found. For all patients, the frequency of HLA-B*52 alleles was higher than for donors. HLA-C*12 allelic group was found more frequent in CLL patients than in donors. HLA-DRB1*15 in CLL patients with SARs was found twice as often as in healthy donors or patients without SARs, while HLA-DRB1*13, oppositely, was found twice as rare. HLA-DRB1*16 was signifi cantly more frequent in patients without SARs, compared with donors and the patients with SARs. No signifi cant differences were found in the HLA-A and HLA-DQB1 loci. Conclusion. The association of two HLA alleles with “unmutated” CLL and two others with CLL bearing prognostically unfavorable SARs was found. HLA typing of expanded samples of CLL patients with different prognosis and course of the disease will provide more information on the mechanisms of antigen selection in the pathogenesis of CLL and improve diagnostic and therapeutic approaches.

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HLA Is a Determinant Of The Ethnic Predisposition Of Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v122.21.1620.1620 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1620-1620

Author(s):

LOREN GRAGERT ◽

Stephanie DiPrima ◽

Mark Albrecht ◽

Martin Maiers ◽

Matt Kalaycio ◽

...

Keyword(s):

African Americans ◽

Chronic Lymphocytic Leukemia ◽

Allele Frequency ◽

Odds Ratio ◽

Lymphocytic Leukemia ◽

Hla Typing ◽

P Values ◽

Hla Alleles ◽

Asian Populations ◽

Allele Family

Abstract Introduction Chronic Lymphocytic Leukemia (CLL) displays remarkable ethnic predisposition for Caucasians with a lower incidence of disease in African Americans and relative sparing of Asian Populations. In addition, CLL displays one of the highest familial predispositions of all hematologic malignancies, yet the genetic basis for these differences is not fully defined. Large scale genome wide association studies (GWAS) of CLL have identified the Human Leukocyte Antigen (HLA) locus and other loci associated with the development of CLL but the contribution of individual HLA alleles has not been extensively examined. The National Marrow Donor Program (NMDP) registry contains a large number of disease cases and donor controls across multiple populations as well as high quality classical HLA typing, making it a powerful source of data for inferring HLA associations for hematologic diseases. Using the NMDP dataset, we report the largest study of the HLA associations for chronic lymphocytic leukemia (CLL) to date. Methods Cases consisted of 2,689 US Caucasian and 298 African-American patients with CLL who underwent HLA typing performed for allogeneic donor search reported to the National Marrow Donor Program (NMDP). 50,000 controls were randomly selected for each population from US individuals who voluntarily enrolled in the NMDP unrelated donor registry. To address ambiguous haplotype phasing inherent to HLA typing, we used population haplotype frequencies to calculate probabilities for genotypes for each possible pair of HLA haplotypes. We then incorporated this typing ambiguity into a statistical model using multiple imputation, allowing us to report high-resolution allele, haplotype, and genotype associations. Patients and controls were compared using multivariate logistic regression using a generalized linear model for the covariates of age, birthdate, gender, and geographical location. To control for multiple testing, we adjusted p-values using False Discovery Rate with a cutoff of 0.05. Results We identified several HLA alleles that are associated with an increased susceptibility to the development of CLL as well as several alleles that are protective in the Caucasian as well as the African American (AA) US population. In Caucasians, A*02:01 (OR = 1.203, p = 0.00053), B*15:01 (OR = 1.264, p = 0.0105), B*38:01 (OR = 1.396, p = 0.0198), DRB1*04:02 (OR = 1.675, p = 0.0006) and DRB1*07:01 (OR = 1.223, p = 0.0006) were predisposing and A*01:01 (OR = 0.849, p = 0.01077), B*08:01 (OR = 0.853, p = 0.0437), B*27:05 (OR = 0.743, p = 0.0356) were protective. For African Americans, we find a different collection of high resolution HLA alleles: B*37:01, B*15:17 and DRB1*09:01 were predisposing to the development of CLL (OR 3.017, 3.089 and 2.144, respectively) with highly statistically significant p-values (0.0344, 0.0344, 0.00057, respectively). At the allele family level, B*44 was found to be protective in both Caucasian (OR = 0.843, p = 0.0115) and AA populations (OR = 0.485, p = 0.0309). The allele family C*07 (OR 0.848, p = 0.0046) was protective in Caucasians while C*04 was protective in AA populations (OR = 0.645, p = 0.0422). Association results also revealed additive effects of individual predisposing alleles within the same haplotype, such as the A*02:01∼C*06:02∼B*13:02∼DRB1*07:01 haplotype, which had a higher odds ratio (OR = 2.2, p = 0.000086) than either A*02:01 or DRB1*07:01. We performed a population risk analysis by applying the currently identified allelic disease associations for Caucasians to the known allele frequency seen in other populations, and determined that HLA allele frequency differences contribute to the lower risk of CLL development for both the AA and Asian populations. Conclusions We have identified several HLA associations that confer increased risk of development of CLL in both U.S. Caucasians and African Americans as well as several protective alleles. These results confirm the previously identified association with HLA*02:01 (OR 1.32, Di Bernardo, et al) with highly similar odds ratio. In addition, we identify many HLA allele associations that have not been previously observed due to low statistical power. Differences in HLA predispositions and HLA allele frequency between Caucasian, AA and Asian populations contribute to the difference in incidence of CLL in these populations and may confer inherent biologic differences due to their impact on immune surveillance. Disclosures: Hill: Celgene: Honoraria, Research Funding.

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Impact of Berberine on the Expression of Apollon Gene in Chronic Lymphocytic Leukemia

Trends in Medical Sciences ◽

10.5812/tms.115983 ◽

2021 ◽

Vol 1 (2) ◽

Author(s):

Niloofar Ghanizade ◽

Maral Hemati ◽

Habib Jaafarinejad ◽

Mehrnoosh Pashaei ◽

Parviz Kokhaei

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Lymphocytic Leukemia ◽

Control Group ◽

Peripheral Blood Mononuclear ◽

Healthy Donors ◽

Blood Mononuclear Cells ◽

The Impact

Background: The incidence of B-chronic lymphocytic leukemia (B-CLL) resulting from the clonal accumulation of apoptosis-resistant malignant B lymphocytes is growing in the adult population of Iran. Inhibitors of apoptosis proteins (IAPs) are considered as factors that can delay the onset of CLL cell apoptosis. Berberine is an isoquinoline alkaloid isolated from Cotridis rhizoma that exhibits anti-tumor activities through various mechanisms. Objectives: In this study, we investigated the impact of berberine on the level of Apollon expression in peripheral blood mononuclear cells (PBMCs) of 12 cases newly diagnosed with CLL and 6 healthy donors. Methods: At first, the level of Apollon expression was assessed in PBMCs of CLL patients compared to the healthy donors. Peripheral blood mononuclear cells were cultured in RPMI-1640 medium with 5% fetal bovine serum (FBS) and 1% penicillin/streptomycin for 48 hours, and the effect of berberine (25 µM) on the level of Apollon expression in CLL patients was assessed and compared to that of healthy donors. Results: We found that the expression level of Apollon was not significantly different between CLL patients and healthy donors (P = 0.640). Moreover, berberine induced no significant differences in Apollon expression as compared to the untreated (control) group (P = 0.545 and P = 0.267 in CLL patients and healthy donors, respectively). Conclusions: Overall, our results suggest that berberine has no direct effect on the expression of Apollon gene in CLL patients, and pro-apoptotic impacts of berberine may be exerted through other mechanisms.

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Comparison of HLA Alleles in Follicular Lymphoma and Chronic Lymphocytic Leukemia Patients Referred for Allogeneic Stem Cell Transplantation

Blood ◽

10.1182/blood.v120.21.4218.4218 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4218-4218

Author(s):

Fleur M. Aung ◽

Benjamin Litchtiger ◽

Issa Khouri

Keyword(s):

Stem Cell ◽

Chronic Lymphocytic Leukemia ◽

Stem Cell Transplantation ◽

Follicular Lymphoma ◽

Cell Transplantation ◽

Normal Population ◽

Lymphocytic Leukemia ◽

Control Group ◽

P Value ◽

Hla Alleles

Abstract Abstract 4218 Introduction: Data recently published showed that besides the several well-known parameters, long term outcome after allogeneic stem cell transplantation (SCT) in chronic lymphocytic leukemia (CLL) may be influenced by the presence or absence of certain HLA class I alleles (HLA-A1+/A2-/B44-) (Khouri et. Al. Cancer 2011). We have also recently published an 11-year progression free survival (PFS) rate of 72% in relapsed follicular lymphoma (FL) after SCT (Khouri et al. Blood 2012). A higher relapse rate has been observed in CLL patients when compared to FL (50% vs. 4%). Since HLA subtypes played an important role in CLL, our goal in this study was to assess and compare over expressed HLA alleles in FL and CLL patients who received a SCT at our center. Methods: Two cohorts of patients who received SCT were retrospectively studied. Group I consisted of 59 Caucasian patients (23 [39%] F: 36 [61%] M) with FL and Group II consisted of 119 Caucasian patients (27 [23%] F: 112 [77%] M) with CLL. The HLA alleles at HLA-A, -B,-C and -DRB1 loci of both groups were analyzed and the HLA typing was performed by polymerase chain reaction (PCR) amplification and oligonucleotide hybridization using commercial kits from Invitrogen (Carlsbad, Ca) or One Lambda (Canoga Park, Ca) that resulted in intermediate resolution. Patients were also typed for these loci using high-resolution methods with PCR amplification and nucleotide sequencing (Abbott, Abbott Park, Ill). The antigen frequencies of all of the alleles of HLA-A, -B,-C AND DRB1 were calculated. Antigen frequency was defined as the percentage of the population possessing the antigen. Antigen frequency comparisons were only done for North American whites due to sample size and control group constraints. The control group was based on a sample analysis of 643 normal North American Whites. The Pearson x2goodness-of-fit test was used to validate the Hardy-Weinberg genetic equilibrium for phenotypic data. The association of various alleles with the control group was determined by using a chi-square test with Yates correction in a 2 × 2 table with 1 degree of freedom (SAS software, version 6.12, SAS Institute Inc, Cary NC). P values < 0.05 at the 95% confidence interval (95% CI) were considered significant. Results: A male predominance was noted in both patient groups. A total of 17 HLA-A, 29 HLA-B, 13 HLA-C and 13 HLA-DRB1 distinct alleles for FL patients and 16 HLA-A, 24 HLA-B, 13 HLA-C and 11 HLA-DRB1 distinct alleles were identified for the CLL patients. Since the predominant ethnic type in both groups were North American Whites, statistically valid comparisons of HLA antigen frequencies were only possible in this population. The observed heterozygosity for FL/CLL patients was 0.93220./0.831932 for HLA-A, 0.915254/0.949579 for HLA-B, 0.779661/0.882352 for HLA-C and 0.847457/0.941176 for HLA-DRB1. There were no untyped patients and all of the patients underwent hematopoietic stem cell transplantation. Our analysis reveals an over expression of HLA-A*03, HLA-C*04, HLA-DRB1*01, HLA-DRB1*07 and HLA-DRB1*15 with frequencies of 25.4%, 24.1%, 22.9%, 28.8% and 8.5 % in FL patients which was significantly higher than the frequencies of 15.1% for HLA-A*03 (p value 0.005), 1.1% for HLA-C*04 (p value < .00001), 10.3% for HLA-DRB1*01 (p value <.0001), 14.4% for HLA-DRB1*07 (p value < .0001) and 15.7% for HLA-DRB1*15 (p value < .0495) in the normal population showing for the first time an over representation of these alleles in patients with FL. In the CLL group our analysis revealed a 24.8% (p value 0.0014) frequency for HLA-A*01 which was significantly higher than the frequency of 16% (p value 0.0014) in the normal population showing an overrepresentation of this allele. The underrepresented allele was HLA-B*38 with a frequency of 3.4% compared to 12.4% (p value 0.0335) in the normal population. When the two groups FL and CLL patients were analyzed, the significant alleles were HLA-A*01, HLA-A*03, HLA-C*04, HLA-DRB1*01 and HLA-DRB1*07. Conclusion: Our results demonstrate a significant difference in HLA expression in Follicular Lymphoma and Chronic Lymphocytic Leukemia patients with the over representation of HLA-A*03, HLA-C*04, HLA-DRB1*01, HLA-DRB1*07 and HLA-DRB1*15 alleles in FL and HLA-A*01 and HLA-B*38 alleles in CLL. We do not know whether these variances account for a different graft-versus-malignancy susceptibility to donor cells between the two groups and this remains to be studied. Disclosures: No relevant conflicts of interest to declare.

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HLA Alleles Repertoire in Russian CLL Patients

Blood ◽

10.1182/blood-2019-123649 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5462-5462

Author(s):

Bella V. Biderman ◽

Ekaterina G Khamaganova ◽

Ekaterina B Likold ◽

Alena R Abdrakhimova ◽

Evgeny A Leonov ◽

...

Keyword(s):

Conflicts Of Interest ◽

Variable Region ◽

The United States ◽

Small Sample ◽

Lymphocytic Leukemia ◽

Hla Typing ◽

Chi Square ◽

Hla Alleles ◽

Mutational Status ◽

Healthy Donors

Introduction. Chronic lymphocytic leukemia (CLL) is one of the most common lymphoproliferative diseases in Europe and the USA. The mutational status of the immunoglobulin heavy chain variable region genes (IGHV) has long been known as an important factor for long-term prognosis in CLL. The variety of the rearranged IGHV structure variants in CLL cells is very limited and differs significantly from that in normal B cells. About 30% of all cases of CLL have immunoglobulin receptors with very similar nucleotide sequences. These quasi-identical receptors are called stereotyped. The most common 20 subtypes of stereotyped antigen receptors (SARs) are presented in 12% of all CLL cases. HLA-complex plays a central role in the formation of the immune response. Associations of specific HLA-alleles with different malignant, autoimmune and infectious diseases have been described. However, possible relationship of HLA phenotype to the development of CLL and the association of HLA alleles with disease are not completely understood. Aim. To study the repertoire of HLA alleles in Russian CLL patients with the most common SARs. Patients and methods. The study included 50 CLL patients with the most common IGHV genes and SARs, followed up at the National Research Center for Hematology from 2008 to 2019. Two groups of healthy donors were selected as control - one from Moscow (1507) and other from Eastern Siberia (296). The mutational status of IGHV and the SARs were determined according to European Research Initiative in CLL (ERIC) criteria. HLA-typing in 5 loci (HLA-A, -B, -C, -DRB1, -DQB1) was performed using Luminex 200 system (Luminex, TX, USA) with Lifecodes HLA SSO typing kits (Immucor, CT, USA). HLA frequencies were compared using chi-square test. ARLEQUIN software package, version 3.5 was used for statistical analysis. Results. All patients enrolled in the study had unmutated IGHV genes. In 43 of them, homology with the germline gene was 100%, and in 7 - it was in the range of 98.6-99.7%. IGHV genes of 46 patients (92%) belonged to the 1st family. In 14 (28%) patients CLL#1 SAR, associated with the most aggressive course of the disease, was expressed. Nine patients (18%) each belonged to the CLL#3 and CLL#6 subtypes. The remaining patients expressed CLL#5, 7H, 12 and 28A SARs. No significant differences in the frequency of HLA-A alleles were found between CLL patients and both donor groups. HLA-B*18, HLA-B*52 and HLA-C*12:02 were found significantly more often in CLL patients than in donors. In the DRB1 locus, differences were observed in the two allelic groups. In CLL patients HLA-DRB1*15 was twice more frequent than in healthy donors, HLA-DRB1*13, on the contrary, was twice less frequent. No significant differences were found for DQB1 locus. Most common HLA haplotype frequencies were also calculated. DRB1*15-DQB1*06 haplotype was significantly 2 times more frequent in CLL patients than in donors. Furthermore, A*02-B*07-C*07-DRB1*15-DQB1*06 and A*25-B*18-C*12-DRB1*15-DQB1* 06 were more frequent, but these data were not statistically significant probably due to the small patient sample (Table 1). No significant differences were found between the SAR subtypes of CLL patients in the studied cohort. Discussion. Despite a small sample, we were able to detect 4 predictive and 1 protective HLA allele for CLL patients. Our data disagree with the data of researchers from the United States and France and partially match those obtained by Iranian scientists. This might be explained by two reasons. First, HLA allele frequencies are differ between various populations. Second, we studied a small selected sample - all patients had unmutated IGHV genes, mainly from the same V gene family, and belonged to a cohort with an aggressive course of the disease. Further studies on extended samples of CLL patients are required to assess possible associations of HLA alleles with CLL subtypes and the course of the disease. Disclosures No relevant conflicts of interest to declare.

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Emergence of a B-cell lymphoblastic lymphoma in a patient with B-cell chronic lymphocytic leukemia: evidence for the single-cell origin of the two tumors

Blood ◽

10.1182/blood.v78.3.797.bloodjournal783797 ◽

1991 ◽

Vol 78 (3) ◽

pp. 797-804

Author(s):

V Pistoia ◽

S Roncella ◽

PF Di Celle ◽

M Sessarego ◽

G Cutrona ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Cell Lines ◽

Peripheral Blood ◽

Chromosomal Abnormalities ◽

Cell Clone ◽

Lymphoblastic Lymphoma ◽

Lymphocytic Leukemia ◽

Terminal Deoxynucleotidyl Transferase ◽

Chain Gene

A patient is described who presented with a chronic lymphocytic leukemia (CLL) and later developed a lymphoblastic lymphoma. The cells from the CLL were typical mature B lymphocytes as could be assessed by morphologic, cytochemical, and surface marker analyses. The cells from the lymphoblastic lymphoma were immature B cells that expressed CD10, CD20, and HLA-DR markers, but not surface Ig or cytoplasmic mu chains, and were negative for terminal deoxynucleotidyl transferase (TdT). The cells of two continuous cell lines, obtained from the bone marrow and the peripheral blood of the patient, had the same phenotype as the lymphoblastic lymphoma cells, did not contain the Epstein-Barr virus genome, and displayed malignant features in vitro, including the capacity to form colonies in agar. The two cell lines also shared identical chromosomal abnormalities, a finding which suggests that they derived from the same malignant cell already present in vivo. Such chromosomal abnormalities were not seen in the karyotype of the peripheral blood cells at the onset of the disease. Analysis of the Ig heavy chain genes using a DJ-specific probe showed the very same monoclonal rearrangement in the cells from the B-CLL, the lymphoblastic lymphoma and the two cell lines, thus demonstrating their common clonal origin. By contrast, a monoclonal rearrangement of the lambda chain gene locus was found in the B-CLL cells only, a finding consistent with their exclusive capacity to express surface IgM lambda. This patient represents a rare case in whom a chronic lymphoproliferative disorder with mature malignant cells transforms into a lymphoblastic lymphoma characterized by cells frozen at a very early maturational stage. The possible mechanisms leading to such transformation within the same cell clone are discussed.

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Akt Inhibitors Induce Apoptosis in Chronic Lymphocytic Leukemia Cells.

Blood ◽

10.1182/blood.v114.22.1731.1731 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1731-1731

Author(s):

Mercè de Frias ◽

Daniel Iglesias-Serret ◽

Ana M Cosialls ◽

Llorenç Coll-Mulet ◽

Antonio F Santidrián ◽

...

Keyword(s):

T Cells ◽

Chronic Lymphocytic Leukemia ◽

Conflicts Of Interest ◽

Therapeutic Option ◽

Mrna Level ◽

Lymphocytic Leukemia ◽

Mrna Levels ◽

Dependent Manner ◽

Healthy Donors ◽

Induced Apoptosis

Abstract Abstract 1731 Poster Board I-757 Phosphatidylinositol-3-kinase (PI3K)/Akt pathway has been described to be critical in the survival of chronic lymphocytic leukemia (CLL) cells. Here, we have analyzed the effect of two selective chemical inhibitors of Akt (Akti-1/2 and A-443654) in the survival of CLL cells. We studied by cytometric analysis the cytotoxic effects of Akt inhibitors on peripheral B and T lymphocytes from patients with CLL and from healthy donors. Both inhibitors induced apoptosis in CLL cells in a dose-dependent manner. Moreover, B cells from CLL samples were more sensitive to Akt inhibitors than T cells from CLL samples, and B or T cells from healthy donors. Survival factors for CLL cells, such as IL-4 and SDF-1a, were not able to block the apoptosis induced by both Akt inhibitors. We studied the changes induced by Akti-1/2 and A-443654 at mRNA level by performing reverse transcriptase multiplex ligation–dependent probe amplification (RT-MLPA). Akti-1/2 did not induce any change in the mRNA expression profile of genes involved in apoptosis, while A-443654 induced some changes, including an increase in NOXA and PUMA mRNA levels, suggesting the existence of additional targets for A-443654. We also studied the changes induced by both Akt inhibitors in some BCL-2 protein family members on CLL cells by Western blot. Both inhibitors induced an increase in PUMA and NOXA protein levels, and a decrease in MCL-1 protein level. Moreover, Akti-1/2 and A-443654 induced apoptosis irrespective of TP53 status. These results demonstrate that Akt inhibitors induce apoptosis of CLL cells and might be a new therapeutic option for the treatment of CLL. Disclosures No relevant conflicts of interest to declare.

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Role of interleukin-10 and interleukin-24 in the pathogenesis of В-cell chronic lymphocytic leukemia

Nauchno-prakticheskii zhurnal «Patogenez» ◽

10.25557/2310-0435.2018.02.56-61 ◽

2018 ◽

pp. 56-61

Author(s):

Т.Н. Жевак ◽

Н.П. Чеснокова ◽

Т.В. Шелехова ◽

О.Е. Царева ◽

И.А. Будник ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Serum Level ◽

B Cell ◽

Serum Levels ◽

Lymphocytic Leukemia ◽

Disease Stage ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Patient Groups ◽

Cell Chronic Lymphocytic Leukemia

Цель. Изучить закономерности изменения экспрессии интерлейкина-10 и интерлейкина-24, обладающих иммуномодулирующим эффектом, при развитии B-клеточного хронического лимфолейкоза. С учетом этого выявить информативные прогностические критерии развития гемобластоза и/или нового подхода к терапии заболевания. Методы. У 120 больных с разными стадиями В-клеточного хронического лимфолейкоза методом твердофазного иммуноферментного анализа исследована динамика уровней интерлейкина-10 и интерлейкина-24 в сыворотке крови. Результаты. Обнаружено закономерное повышение содержания интерлейкина-10 и интерлейкина-24 в сыворотке крови пациентов уже на начальной стадии B-клеточного хронического лимфолейкоза и сохранение их достоверно высоких уровней на последующих стадиях заболевания. Заключение. Обнаруженный нами факт повышения содержания интерлейкина-10 в сыворотке крови пациентов с В-клеточным хроническим лимфолейкозом является фактором риска снижения противоопухолевой защиты организма вследствие подавления им механизмов клеточного иммунитета и способности ингибировать апоптоз малигнизированных клеток. Напротив, повышение экспрессии интерлейкина-24, обладающего проапоптотической активностью и стимулирующего дифференцировку клеток, может способствовать повышению эффективности механизмов противоопухолевой резистентности организма. Устранение дисбаланса продукции и/или содержания указанных цитокинов в сыворотке крови может создать условия повышения эффективности терапии пациентов с В-клеточным хроническим лимфолейкозом. Aim. To study serum levels of immunosuppressive cytokines (interleukin (IL)-10 and IL-24) in patients with B-cell chronic lymphocytic leukemia for assessment of the disease progression and elaboration of a new treatment strategy. Methods. 120 patients with B-cell chronic lymphocytic leukemia were enrolled in the study and divided into four groups according to the disease stage (Rai stage I-IV). Control group included 30 healthy volunteers. Concentrations of IL-10 and IL-24 were measured in serum using the enzyme-linked immunosorbent assay (ELISA). Results. Serum levels of IL-10 and IL-24 levels were significantly increased in all patient groups compared to the control. No difference in the cytokines levels between the patient groups was observed. Conclusion. In patients with B-cell chronic lymphocytic leukemia, the increased serum level of IL-10 might impair the antitumor defence by inhibiting the cell immune response and preventing apoptosis of malignant lymphocytes. On the other hand, the increased serum level of IL-24 might oppose these effects by promoting cellular differentiation and inducing apoptosis in malignant cells. Therefore, correction of IL-10/IL-24 imbalance may be a beneficial therapeutic strategy for patients with B-cell chronic lymphocytic leukemia.

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