Linfocitosis monoclonal de células B en familiares de pacientes colombianos con síndromes linfoproliferativos crónicos B

Introducción. La linfocitosis monoclonal de células B, generalmente, precede la leucemia linfocítica crónica y afecta alrededor del 12 % de la población adulta sana. Esta frecuencia se incrementa en familiares de pacientes con síndromes linfoproliferativos crónicos de células B. Objetivo. Determinar la frecuencia de linfocitosis monoclonal B en familiares de pacientes con síndromes linfoproliferativos crónicos B, sus características inmunofenotípicas y citogenéticas, posible relación con agentes infecciosos, y seguimiento a corto plazo de población colombiana. Materiales y métodos. Se estudiaron 50 adultos sanos con antecedentes familiares de síndromes linfoproliferativos crónicos de célula B, empleando citometría de flujo multiparamétrica, pruebas citogenéticas y serológicas, encuesta de hábitos de vida y seguimiento a dos años. Resultados. La frecuencia encontrada de linfocitosis monoclonal B fue del 8 %, con predominio del sexo femenino y edad avanzada, incrementándose al 12,5 % en individuos con antecedentes familiares de leucemia linfocítica crónica. Tres de cuatro individuos presentaron inmunofenotipo de tipo leucemia linfocítica crónica, todas con bajo recuento. A su vez, en estos individuos se observa de manera significativa un mayor número de células/ µl en subpoblaciones linfocitarias T, junto con mayor predisposición a la enfermedad. Las poblaciones clonales descritas aumentan a lo largo del tiempo de manera no significativa. Conclusiones. La frecuencia y comportamiento de la linfocitosis monoclonal de célula B en pacientes con antecedentes familiares de síndromes linfoproliferativos crónicos B es similar a lo encontrado en estudios relacionados, lo que sugiere que no existe afectación de genes de mayor relevancia que puedan desencadenar una proliferación clonal descontrolada, pero que generan desregulación inmunológica que podría indicar un mayor riesgo de infección grave en estos individuos.

Introduction. Monoclonal B-cell lymphocytosis generally precedes chronic lymphocytic leukemia, affecting about 12% of the healthy adult population. This frequency increases in relatives of patients with chronic B-cell lymphoproliferative disorders. Objective. To determine the frequency of monoclonal B-cell lymphocytosis in relatives of patients with chronic B-cell lymphoproliferative disorders, their immunophenotypic/ cytogenetic characteristics, a possible relationship with infectious agents, and short-term follow-up in the Colombian population. Materials and methods. Fifty healthy adults with a family history of chronic B-cell lymphoproliferative disorders were studied using multiparametric flow cytometry, cytogenetic/serological testing, lifestyle survey, and 2-year follow-up. Results. The frequency of monoclonal B-cell lymphocytosis found was 8%, with a predominance of female gender and advanced age, increasing to 12.5% for individuals with a family history of chronic lymphocytic leukemia. Three out of four individuals presented chronic lymphocytic leukemia-type immunophenotype, all with low counts. In turn, a significantly higher number of cells/µΙ is observed in these individuals in T lymphocyte subpopulations, together with a greater predisposition to the disease. The described clonal populations increase over time in a non-significant manner. Conclusions. The frequency and behavior of monoclonal B-cell lymphocytosis in patients with family history of chronic B-cell lymphoproliferative disorders are like those found in related studies, which suggests that there is no involvement of more relevant genes that can trigger uncontrolled clonal proliferation, but that generates immunological deregulation that could justify a greater risk of serious infection in these individuals.

Diagnostic efficacy comparison between CLLflow score and Moreau score for chronic lymphocytic leukemia / 中华检验医学杂志

Objective:To explore the diagnostic efficacy difference and clinical diagnostic value of chronic lymphocytic leukemia flow (CLLflow) score and Moreau score (MS) in the diagnosis of chronic lymphocytic leukemia (CLL).Methods:According to the latest international and national diagnosis criteria for CLL, 133 patients with B-cell chronic lymphoproliferative diseases and uncertain immunophenotypes (B-CLPD), diagnosed by Zhengzhou Jinyu Comprehensive Haematological Pathology Diagnosis Centre from March 2020 to May 2021, were included in this study. Above patients were divided into the CLL group ( n=83) and non-CLL group ( n=50). The expression of clusters of differentiation (CD)5, CD10, CD20, CD19, κ light chain, λ light chain, FMC7, CD23, CD22, surface immunoglobulin M, CD200 and CD79 were detected by flow cytometry, and CLLflow score and MS score were calculated respectively according to the scoring rules. A fourfold table was used to compare the diagnostic efficacy of the two scoring systems, and the Kappa test and McNemar test were used to compare the consistency and superiority of the systems. Results:The rate of negative and positive CLLflow score were 4.8% (4/83) and 95.2% (79/83) in the CLL group and were 80.0% (40/50) and 20.0% (10/50) in the non-CLL group, and respectively (both P<0.001). The MS score (≤2, =3 and≥4) was 1.2% (1/83), 10.8% (9/83) and 88.0% (73/83) in the CLL group and was 86.0% (43/50), 14.0% (7/50) and 0 in the non-CLL group, there were significant statistical difference between the two groups ( P<0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the CLLflow score were 95.2% (79/83), 80.0% (40/50), 88.8% (79/89) and 90.9% (40/44), respectively and those of MS score were 98.8% (82/83), 86.0% (43/50), 92.1% (82/89) and 97.7% (43/44) respectively. The overall coincidence rate, positive and negative coincidence rate between the CLLflow score and MS score were 91.0% (121/133), 93.3% (83/89) and 86.4% (38/44) respectively. Besides, the McNeamr dominance test presented no significant difference ( P>0.05) and high consistency (Kappa=0.796) between the two scoring systems. With MS≤2 and MS≥4, the sensitivity and the specificity of the MS score were 100% (73/73) and 97.7% (43/44) respectively, and for the CLLflow score, the sensitivity and the specificity were 97.3% (71/73) and 86.4% (38/44) in this MS range. With MS = 3, the sensitivity and specificity of the MS score were 100% (9/9) and 0 (0/7), and CLLflow was 88.9% (8/9) and 57.1% (4/7). Conclusions:The diagnostic efficacy is similar and presents high consistency between the CLLflow score and MS score in CLL diagnosis. For CLL patients with MS = 3, the specificity of MS is relatively low, combined assessment with CLLflow score could improve the diagnosis efficacy for CLL in these patients.

Chronic lymphocytic leukemia with nephrotic syndrome as the initial manifestation: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical manifestation, diagnosis and treatment of chronic lymphocytic leukemia patients with renal involvement.Methods:The clinical data of a chronic lymphocytic leukemia patient with nephrotic syndrome as the initial manifestation in Fujian Provincial People's Hospital in October 2020 were retrospectively analyzed, and the related literature was reviewed.Results:The patient was a 68-year-old male with recurrent edema and foam urine as the initial manifestations, and he was diagnosed as nephrotic syndrome in the nephrology department. After treatment, the symptoms showed no significant improvement, and the lymphocyte count gradually increased. The patient was diagnosed as chronic lymphocytic leukemia in the hematology department. After ibrutinib monotherapy, the lymphocyte count and urine protein gradually decreased to normal levels, and the clinical efficacy evaluation of the patient was complete remission at the end of follow-up.Conclusions:Chronic lymphocytic leukemia with nephrotic syndrome as the initial manifestation is rare, and the clinical presentations are variable. Early diagnosis is the guarantee of successful treatment. The efficacy and safety of first-line Bruton tyrosine kinase inhibitor monotherapy are good.

Diagnostic and prognostic value of ROR1 antigen in patients with chronic lymphocytic leukemia / 中华检验医学杂志

Objective:To detect the expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) antigen in chronic lymphocytic leukemia (CLL) and evaluate its diagnostic value and explore its correlation with the abnormalities of genetics and molecular biology.Methods:All of 209 newly diagnosed B-cell chronic lymphoproliferative disorders (B-CLPD) patients who were admitted to the First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People′s Hospital) from November 2020 to November 2021 were collected retrospectively, including 70 cases of CLL with typical phenotype, 16 cases of CLL with atypical phenotype, 14 cases of MCL, and 109 cases of other types of B-CLPD. Multi-parameter flow cytometry (FCM) was used to detect the expression levels of ROR1 in tumor cells of 209 patients. And then the diagnostic value of ROR1 in CLL patients and its correlation with the genetic and molecular biological abnormalities were analyzed by c2 test and fourfold table assessment.Results:The positive expression rate of ROR1 in CLL patients was significantly higher than that in non-CLL patients (78%>11%, P<0.001); there was no significant difference of ROR1 expression between typical phenotype CLL and atypical phenotype CLL (81%>63%, P>0.05). The positive expression rate of ROR1 in atypical phenotype CLL was significantly higher than that in MCL (63%>21%, P<0.05). Additionally, there was significant difference in detection rate of chromosomal abnormalities between ROR1 +CLL group and ROR1 -CLL group. The detection rate of complex karyotype in ROR1 +CLL group was higher than that in ROR1 -CLL group (34%>14%, P<0.05). The CLL patients over 60 years old had higher ROR1 positive rate ( P<0.05). Conclusions:ROR1 can be helpful in the diagnosis of CLL, especially in the differential diagnosis of atypical phenotype CLL, MCL and other types of B-CLPD. Patients with ROR1 positive expression were older and more likely to detect complex chromosomal karyotypes.

Diagnostic value of 18F-FDG PET/CT for Richter syndrome of chronic lymphocytic leukemia / 中华核医学与分子影像杂志

Objective:To explore the value of 18F-FDG PET/CT in detecting Richter syndrome (RS) in chronic lymphocytic leukemia (CLL) patients. Methods:From August 2010 to November 2019, 101 histologically confirmed CLL patients (62 males, 39 females; age (58.0±12.7) years) who underwent PET/CT in Nanjing Drum Tower Hospital and the First Affiliated Hospital of Nanjing Medical University were retrospectively included. ROI was drawn and PET/CT images were semi-quantitatively examined by estimating SUV max. Mann-Whitney U test was used to compare the SUV max of RS and non-RS patients. ROC curve analysis was utilized to analyze the optimal cut-off value of SUV max in detecting RS. Results:RS was histologically confirmed in 27 CLL patients. The SUV max of RS patients was 13.7(11.0, 20.1), which was significantly higher than that of non-RS patients (4.1(3.1, 5.8); z=-6.48, P<0.001). ROC curve analysis identified the optimal cut-off value of SUV max was 10.0 and the AUC was 0.923, with accuracy of 94.1%(95/101), sensitivity of 85.2%(23/27), specificity of 97.3%(72/74), positive predictive value of 92.0%(23/25) and negative predictive value of 94.7%(72/76). Conclusion:As the semi-quantitative index measured by 18F-FDG PET/CT, SUV max can help to diagnose RS and provide important information for clinical use.

Leucemia linfocítica crónica y deleción del gen TP53: reporte de un caso y revisión de la literatura / Chronic lymphocytic Leukemia and deletion of the TP53 gene: Case report and literature review

RESUMEN Las alteraciones genéticas en el gen TP53 están presentes entre el 5 al 8 % de los pacientes de leucemia linfocítica crónica (LLC) en el momento del diagnóstico. Estos casos se relacionan con un mal pronóstico debido a su resistencia al tratamiento estándar. Presentamos el caso de un paciente masculino de 52 años diagnosticado con LLC, expresión del marcador CD38 y una deleción en el gen TP53 (17p13.1). Tras la evaluación posterior del tratamiento, se observó enfermedad mínima residual lo que llevó a un trasplante haploidéntico de progenitores hematopoyéticos. Debido al alto riesgo de recaída, su edad y la ausencia de comorbilidades, era la única opción curativa hasta la fecha para la LLC. El objetivo de este trabajo es realizar una revisión de la literatura que sirva como base para analizar el caso clínico presentado, en el marco de las implicaciones clínicas, pronóstico y respuesta al tratamiento en los individuos con LLC que presentan alteraciones en el gen TP53.

SUMMARY Genetic alterations in the TP53 gene are present in 5 to 8% of chronic lymphocytic leukemia (CLL) cases at the time of diagnosis. These cases are typically associated with poor prognosis due to their resistance against standard CLL treatment. In our report a 52-yearold male patient was diagnosed with CLL, CD38 expression and a deletion in the TP53 gene (17p13.1). Upon evaluation post-treatment, minimal residual disease (MDR) was observed, and a haploidentical stem cell transplant was performed. Because of the high risk of relapse, his age, and the absence of comorbidities it was the only curative option to date for CLL. The purpose of this article is to complete a literature review that will give a basis to analyze the clinical case presented, within the framework of the clinical implications, prognosis, and response to treatment in patients with CLL who present with aberrations of the TP53 gene.

Progress of immunotherapy in chronic lymphocytic leukemia / 白血病·淋巴瘤

Chronic lymphocytic leukemia (CLL) is a heterogeneous, mature B-cell clonal malignancy that mainly affects the senior. The immunotherapies such as chimeric antigen receptor T cell therapy, bi/tri-specific cell binding agent, immune check point therapy, etc., pave several new avenues for CLL treatment, especially the combined applications of new and existing therapies have shown improved efficacy and safety. This article attempts to review the immunotherapies and their combinatorial applications in CLL.

Treatment progress of chronic lymphocytic leukemia / 白血病·淋巴瘤

Chronic lymphocytic leukemia (CLL) is a kind of B-cell chronic lymphoproliferative disease. At present, the common clinical treatment regimens (such as FCR, BR, ibrutinib, etc.) have showed good therapeutic effects, but recurrence and progression still occur in some patients. In order to further improve the efficacy, the new combination therapies for CLL are continuously emerging. This article summarizes the treatment progress of CLL in combination with the related reports at the 62nd American Society of Hematology Annual Meeting.

Acquired reactive perforating collagenosis in association with prostate adenocarcinoma, chronic lymphocytic leukemia, and Graves disease

Abstract Acquired reactive perforating collagenosis is a rare skin disorder characterized by the presence of umbilicated pruritic papules and nodules. Transepidermal elimination of altered and perforating bundles of basophilic collagen from the epidermis is a characteristic histologic feature of acquired reactive perforating collagenosis. Along with its well-known association with systemic diseases such as diabetes mellitus, chronic renal failure, and dermatomyositis, there are reports of acquired reactive perforating collagenosis being associated with malignancies. Herein, we present a case of acquired reactive perforating collagenosis associated with chronic lymphocytic leukemia, prostate adenocarcinoma, and Graves's disease. Clinicians are required to be more vigilant in evaluating patients with acquired reactive perforating collagenosis due to its unique association with malignancies and other systemic diseases.

Chronic lymphocytic leukemia complicated with multiple myeloma: report of one case and review of literature / 白血病·淋巴瘤

Objective@#To investigate the clinical features, diagnosis, occurrence sequence and clonal origin of chronic lymphocytic leukemia complicated with multiple myeloma.@*Methods@#The diagnosis and treatment of one patient with multiple myeloma and chronic lymphocytic leukemia who was admitted to the First Hospital of Jilin University in May 2018 was retrospectively analyzed, and the related literatures were reviewed.@*Results@#This patient began with lumbosacral pain, and he was diagnosed as chronic lymphocytic leukemia complicated with multiple myeloma after bone marrow aspiration, flow cytometry, and blood and urine immunofixation electrophoresis. It is recommended that Rd (lenalidomide + dexamethasone) or MPV (melphalan + prednisone + bortezomib) regimen, but the patient did not receive chemotherapy and died of infectious diarrhea 1 month later.@*Conclusions@#The occurrence of multiple myeloma and chronic lymphoblastic leukemia may originate from the same clone or different new clone. It is very rare that multiple myeloma and chronic lymphoblastic leukemia can co-occur. Therapeutic options tend to be more aggressive multiple myeloma-based regimen.

High-grade B-Cell lymphoma with MYC and BCL6 rearrangements associated with Richter transformation of chronic lymphocytic leukemia

Richter transformation (RT), or Richter syndrome, is defined as the transformation of chronic lymphocytic leukemia (CLL) to an aggressive B-cell lymphoma. The vast majority, up to 99%, transform into diffuse large B-cell lymphoma (DLBCL), with a small subset (<1%) becoming classical Hodgkin lymphoma. Approximately half of RT cases progress through a pathway involving dysregulation of C-MYC. High-grade B-cell lymphoma (HGBL) is a recent diagnostic category of aggressive B-cell lymphomas set forth in the updated 2017 WHO Classification of Hematopoietic and Lymphoid Tissues. HGBL with MYC and BCL2 and/or BCL6 rearrangements, formerly "double-hit" and "triple-hit" lymphomas, comprise the majority of HGBL cases. Patients with HGBL have a worse prognosis than those with diffuse large B-cell lymphoma. We present a case of RT with rearrangements of MYC and BCL6. To our knowledge, there are no reported cases of RT with a "double-hit" lymphoma genotype.

Clinical research progress of ibrutinib in the treatment of chronic lymphocytic leukemia / 中国基层医药

Chronic lymphocytic leukemia(CLL) is a heterogeneous mature B lymphocytic tumor.The apoptosis of mature lymphocyte is inhibited and clonal proliferation of mature lymphocyte aggregates in blood, bone marrow, spleen and lymph nodes, resulting in a class of inert hematological tumors.At present, the clinical pathogenesis is not completely clear, environmental and occupational factors do not occupy a major position.Studies have shown that long-term exposure to low-frequency electromagnetic fields may be associated with its incidence, but patients with primary and secondary relatives of lymphatic malignancies increased incidence.Many families still have patients whose age is earlier and the disease is more serious.In recent years, with the continuous improvement of medical level, a variety of treatment methods for chronic lymphoblastic leukemia have emerged, including a variety of new drugs.Ibutinib is the world's first marketed Bruton's tyrosine kinase(BTK) inhibitor, for more patients with chronic lymphoblastic leukemia has brought the gospel.This article reviews the clinical research progress of ibrutinib in treating CLL.

High-dose methylprednisolone with Rituximab and fresh frozen plasma in the treatment of six patients with B-cell lymphoproliferative disorders harboring TP53 abnormalities / 中华血液学杂志

Objective@#To investigate whether high-dose methylprednisolone with Rituximab and fresh frozen plasma (HDMP+RTX+FFP) is an effective therapy for patients with B-cell chronic lymphoproliferative disorders (B-CLPD) with TP53 abnormalities.@*Methods@#Six B-CLPD patients with TP53 abnormalities from May 2008 to May 2012 were prospectively enrolled in the study. The patients were treated with HDMP+RTX+FFP for up to 6 cycles.@*Results@#Of the six B-CLPD patients, there were 4 cases of chronic B-cell lymphoproliferative disorders-unclassified (B-CLPD-U) , 1 B-cell prolymphocytic leukemia (B-PLL) and 1 mantle cell lymphoma (MCL) . After a median 3 courses of treatment, 4 patients achieved complete remission (CR) including 3 with undetectable minimal residual disease (MRD-) . One patient was evaluated as stable disease (SD) and another one patient was in disease progression (PD) . After a median follow-up of 30 (4-56) months, 2 non-responders progressed quickly and died. All of CR patients survived and no one succumbed to disease progression at the last follow-up. The hematopoietic function was significantly improved after the treatment whereas there was also significant decrease in serum IgA, IgG and IgM levels. All patients showed well tolerance to this regimen. The incidence of myelosuppression was low and adverse events (AE) were mainly neutropenia which did not exceed grade 3 and infection. All AE were controllable.@*Conclusion@#HDMP+RTX+FFP is an effective and relatively tolerable therapy for patients with B-CLPD accompanying with TP53 abnormalities.

Clinical research progress of ibrutinib in the treatment of chronic lymphocytic leukemia / 中国基层医药

Chronic lymphocytic leukemia(CLL) is a heterogeneous mature B lymphocytic tumor.The apoptosis of mature lymphocyte is inhibited and clonal proliferation of mature lymphocyte aggregates in blood,bone marrow,spleen and lymph nodes,resulting in a class of inert hematological tumors.At present,the clinical pathogenesis is not completely clear,environmental and occupational factors do not occupy a major position. Studies have shown that long -term exposure to low-frequency electromagnetic fields may be associated with its incidence,but patients with primary and secondary relatives of lymphatic malignancies increased incidence. Many families still have patients whose age is earlier and the disease is more serious.In recent years,with the continuous improvement of medical level,a variety of treatment methods for chronic lymphoblastic leukemia have emerged,including a variety of new drugs.Ibutinib is the world＇s first marketed Bruton＇s tyrosine kinase(BTK) inhibitor,for more patients with chronic lymphoblastic leukemia has brought the gospel.This article reviews the clinical research progress of ibrutinib in treating CLL.

Histoplasmosis diseminada como manifestación inicial del linfoma linfocítico de células pequeñas / Disseminated histoplasmosis as a first clinical manifestation in a patient with small lymphocytic lymphoma: A case report

RESUMEN El linfoma linfocítico de células pequeñas es una neoplasia de células B maduras con un amplio espectro de presentaciones clínicas. Las infecciones por gérmenes oportunistas no asociadas con el tratamiento, incluso en estadios avanzados de la enfermedad, tienen baja incidencia. Se han reportado muy pocos casos de pacientes con linfoma linfocítico de células pequeñas asociado a histoplasmosis diseminada que no habían recibido quimioterapia en el momento del diagnóstico. Se presenta el caso de una paciente de 82 años que fue hospitalizada por presentar tos seca intermitente, astenia y adinamia de un mes de evolución. Se le practicaron múltiples estudios para detectar infecciones o compromiso inmunológico o reumático, y se diagnosticó un síndrome adenopático extenso con compromiso cervical, torácico y retroperitoneal. En la citometría de flujo y en la biopsia de ganglio linfático cervical, se reportaron los fenotipos CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg y CD10neg, con restricción de la cadena ligera kappa, lo cual confirmó un linfoma linfocítico de células pequeñas. En la histopatología del ganglio, se observaron granulomas epitelioides sin necrosis, pero las coloraciones especiales no mostraron la presencia de microorganismos, en tanto que el cultivo del ganglio fue positivo para Histoplasma capsulatum. Se inició el tratamiento antifúngico con anfotericina B e itraconazol, y la paciente tuvo una adecuada evolución. Dado que no se cumplían los criterios para el tratamiento oncológico, se continuó con su observación mediante controles periódicos. Las infecciones oportunistas pueden ser la manifestación clínica inicial en pacientes con síndromes linfoproliferativos de bajo grado. Este caso demuestra que pueden desarrollarse, incluso, en ausencia de quimioterapia.

ABSTRACT The small lymphocytic lymphoma is a mature B cell neoplasm with a broad spectrum of clinical presentations. Opportunistic infections that are not related to the treatment, even in advanced stages, have a low incidence rate. There are few case reports in the medical literature of patients who have not received immunosuppressive therapy and present with small lymphocytic lymphoma associated with disseminated histoplasmosis at diagnosis. A female 82-year-old patient was admitted due to an intermittent dry cough, asthenia, and adynamia that had persisted for one month. Multiple studies to detect infections and immuno-rheumatic conditions were performed and an extensive cervical, thoracic and peritoneal adenopathic syndrome was diagnosed. A flow cytometry and a cervical lymph node biopsy were performed reporting CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg, and CD10neg phenotypes with restriction in the light kappa chain compatible with a small lymphocytic lymphoma. Epithelioid granulomas without necrosis were observed in the lymph node histopathology and special colorations showed no microorganisms. The culture from the lymph node was positive for Histoplasma capsulatum. We initiated treatment with amphotericin B and itraconazole with an adequate response. In the absence of compliance with oncology treatment criteria, the patient was managed on a "watch and wait" basis. Opportunistic infections could be the initial clinical manifestation in patients with low-grade lymphoproliferative syndromes. This case report shows that they can develop even in the absence of chemotherapy.

Progress of myeloid differentiation factor 88 L265P mutation in B-cell proliferative neoplasms / 白血病·淋巴瘤

Myeloid differentiation factor 88 (MYD88) is a key linker in the Toll-like receptor (TLR) signaling pathway, which plays an important role in the progression of the tumour. Recent studies have shown that the activating mutation of MYD88 L265P has been identified in about of 90% lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia and about of 40% diffuse large B-cell lymphoma and other subtypes of B-cell proliferative neoplasms. Different types of B-cell proliferative neoplasms have their own histology, immunohistochemistry and clinical characteristics, thus, mutation rates of MYD88 L265P are different. This review discusses the latest progress of MYD88 L265P mutation in B-cell proliferative neoplasms.

Prognostic significance of CLL-IPI for Chinese patients with chronic lymphocytic leukemia / 中华血液学杂志

Objective@#To validate the prognostic value of chronic lymphocytic leukemia-international prognostic index (CLL-IPI) for Chinese CLL patients.@*Methods@#Two hundred and fifteen CLL patients who were initially diagnosed and treated in Jiangsu Province Hospital from January 2002 to November 2017 were included in the retrospective analysis. Risk stratification and prognosis were evaluated by CLL-IPI scoring system.@*Results@#①Of the 215 patients, 143 were males and 72 were females, with a median age of 60 (16-85) years old. The median treatment-free survival (TFS) and overall survival (OS) was 16 months (4-24 months) and 180 months (145-215 months), respectively. ② The median TFS for low (n=60), intermediate (n=50), high (n=45) and very high risk group (n=60) according to the CLL-IPI scoring system was 56, 15, 12 and 5 months, respectively (P<0.001). ③ The median follow-up was 48 months (1-192 months). The median OS for low risk group was not reached and for intermediate, high, and very high risk group was 180, 89 and 74 months, respectively. The estimated 5-year OS rate was 97.6%, 83.7%, 67.8% and 55.2%, respectively (P<0.001). ④ Multivariate analysis indicated that unmutated immunoglobulin heavy chain variable region (IGHV) gene and β2-microglobulin>3.5 mg/L(P<0.001) were independent prognostic factors of TFS, while TP53 deletion and/or mutation(P=0.008), unmutated IGHV (P=0.017) and age>65 years(P=0.045) were independent prognostic factors of OS.@*Conclusion@#CLL-IPI is the powerful tool for risk stratification in Chinese CLL patients.

The expression and prognostic significance of microRNA-34a in Uygur and Han patients with chronic lymphocytic leukemia in Xinjiang Uygur Autonomous Region in China / 中华内科杂志

To investigate the expression of microRNA-34a (miR-34a) in patients with chronic lymphocytic leukemia (CLL) in Xinjiang Uygur and Han nationalities and its prognostic significance. Our data showed that miR-34a expression in Uygur and Han CLL patients was significantly higher than that in their respective healthy controls, while miR-34a levels were similar between Uygur and Han patients. By comparing with known prognostic factors, receiver operating characteristic (ROC) curves showed that miR-34a was a good predictive factor for the prognosis of CLL (demarcation value was 3.567 6). Survival analysis was further performed according to miR-34a expression level, that low expression of miR-34a translated into poor prognosis.

Study on the expression of TRIP13 mRNA in chronic lymphocytic leukemia B lymphocyte and the molecular mechanism of TRIP13 mediated JVM-2 cell proliferation and apoptosis / 中华血液学杂志

Objective@#To investigate the clinical significance of expression level of thyroid hormone receptor interactors 13 (TRIP13) gene to probe its function and downstream molecular mechanism in chronic lymphocytic leukemia (CLL) .@*Methods@#Real-time quantitative PCR method was used to detect the expression levels of TRIP13 mRNA of CD19+ B lymphocytes in 30 cases of patients with CLL and 12 cases of peripheral blood hematopoietic stem cell donors (normal control group) . Lentivirus mediated shRNA was used to interference the mRNA and TRIP13 protein in CLL cells JVM-2. Scramble sequence was used as control. Methyl thiazolyl tetrazolium colorimetric assay (MTT) and flow cytometry was used to detect the cell proliferation and apoptosis in TRIP13 knocked-down and negative control JVM-2 cells.@*Results@#TRIP13 mRNA level was significantly higher in 30 cases of CLL patients (2-△Ct= 0.014 89) compared with 12 healthy donors (2-△Ct= 0.000 19) (P<0.001) . Validated TRIP13 shRNA target was achieved in JVM2 cell. Compared with the control group, down-regulation of TRIP13 expression could significantly inhibit the proliferation of JVM-2 cells and induce apoptosis. The expressions of Myc and Bcl-2 protein in JVM-2 cells decreased significantly after interference with TRIP13 (P<0.001) , and the expressions of Bax, caspase 3 and Bad protein increased significantly (P<0.001) .@*Conclusion@#TRIP13 mRNA significantly over-expressed in CLL patients CD19+ B lymphocytes. TRIP13 could influence JVM2 cell proliferation and apoptosis through proliferation- and apoptosis-related proteins.

PD-1/PD-L1 expression and its implications in patients with chronic lymphocytic leukemia / 中华血液学杂志

Objective@#To observe the expression levels of PD-1/PD-L1 costimulatory molecules and explore the clinical significance in patients with chronic lymphocytic leukemia (CLL) .@*Methods@#The expression of PD-1/PD-L1 in peripheral blood CD8+ T cells, CD4+T cells, CD19+B, and dendrites cells (DC) was detected by flow cytometry in 57 CLL patients and 20 healthy controls. The correlations of PD-1/PD-L1 expression with disease stage, CD38 expression, ZAP-70 expression, chromosome karyotype abnormality and β2-MG expression were analyzed.@*Results@#①Compared with control, CLL patients, including 39 males and 18 females with the median age of (63.7±10.7) years, had no statistically significant difference in age and gender (P>0.05) . CLL patients had the higher PD-1/PD-L1 expression than healthy controls (P<0.05) . ②In Rai staging, the later the stage, the higher expression of PD-1/PD-L1 (P<0.05) . ③PD-1 expression in CD8+CD38+ group (11 cases) was higher than that in CD8+CD38- group (46 cases) (P=0.004) , and CD8+ poor prognosis chromosome group (14 cases) also had significant higher PD-1 expression than CD8+good prognosis chromosome group (28 cases) (P=0.004) . ④The expression of PD-L1 was higher in CD38+group, ZAP-70+group, and poor prognosis group, as compared to that in CD38-group (P=0.002) , in ZAP-70-group (P<0.001) , in good prognosis group (P=0.023) . There was no correlation between the expression of PD-1/PD-L1 and β2-MG (P>0.05) .@*Conclusion@#This data reveals that PD-1/PD-L1 was highly expressed in CLL patients. Its expression levels were correlated with Rai stage, CD38, ZAP-70, chromosome karyotype, but not with β2-MG. PD-1/PD-L1 may be a prognostic factor in patients with CLL.