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1.
Hematol., Transfus. Cell Ther. (Impr.) ; 44(1): 63-69, Jan.-Mar. 2022. tab, graf, ilus
Article in English | LILACS | ID: biblio-1364896

ABSTRACT

Abstract Objective We evaluated the relevance of using the smudge cell percentage in the blood smear as a prognostic marker in CLL. Methods In this prospective study, 42 untreated Senegalese patients with CLL were enrolled. The diagnosis was established, based on the peripheral blood count and flow cytometry using the Matutes score. Cytogenetic aberrations, assessed by fluorescence in situ hybridization (FISH), were available for 30 patients, while the immunoglobulin heavy chain genes (IGVH) mutation status was performed by next-generation sequencing (NGS) in 24 patients. The SC percentage was determined in the blood smear, as previously described. Statistical analyses were executed using the GraphPad Prism 8. Results The mean age was 63 years (48 - 85) and the male: female sex ratio was 4.66. A low SC (< 30%) percentage was correlated with Binet stage B/C (p= 0.0009), CD38 expression (p= 0.039), unmutated IGVH status (p= 0.0009) and presence of cytogenetic abnormalities (for del 13q, p= 0.0012, while for other cytogenetic aberrations, p= 0.016). An inverse correlation was found between the SC percentage and the absolute lymphocyte count (r= -0.51) and patients with higher percentage of SCs had a prolonged survival. However, there was no correlation between the SC percentage and age (p= 0.41) or gender (median, 19% for males vs. 20% for females; p= 0.76). Conclusion When less than 30%, the SC was associated with a poor prognosis in CLL. Easy and affordable, the percentage of SCs in a blood smear could be a reliable prognostic marker, accessible to all CLL patients, mainly those in developing countries.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Leukemia, Lymphocytic, Chronic, B-Cell , Prognosis , Senegal
2.
Iatreia ; 34(4): 370-374, oct.-dic. 2021. graf
Article in Spanish | LILACS | ID: biblio-1350837

ABSTRACT

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.


Subject(s)
Humans , Leukemia, Lymphocytic, Chronic, B-Cell , Genes, p53 , Research Report
4.
Electron. j. biotechnol ; 52: 1-12, July. 2021. tab, ilus, graf
Article in English | LILACS | ID: biblio-1283167

ABSTRACT

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is a neoplasm of B-cells characterized by variable prognosis. Exploring the proteome of CLL cells may provide insights into the disease. Therefore, eleven proteomics experiments were conducted on eleven primary CLL samples. RESULTS: We reported a CLL proteome consisting of 919 proteins (false discovery rate (FDR) 1%) whose identification was based on the sequencing of two or more distinct peptides (FDR of peptide sequencing 1%). Mass spectrometry-based protein identification was validated for four different proteins using Western blotting and specific antibodies in different CLL samples. Small sizes of nucleolin (~57 kDa and ~68 kDa) showed a potential association with good prognosis CLL cells (n = 8, p < 0.01). Compared with normal B-cells, CLL cells over-expressed thyroid hormone receptor-associated protein 3 (THRAP3; n = 9; p = 0.00007), which is implicated in cell proliferation; and heterochromatin protein 1-binding protein 3 (HP1BP3; n = 10; p = 0.0002), which promotes cell survival and tumourogenesis. A smaller form of HP1BP3, which may correspond to HP1BP3 isoform-2, was specifically identified in normal B-cells (n = 10; p = 0.0001). HP1BP3 and THRAP3 predicted poor prognosis of CLL (p 0.05). Consistently, THRAP3 and HP1BP3 were found to be associated with cancer-related pathways (p 0.05). CONCLUSIONS: Our findings add to the known proteome of CLL and confirm the prognostic importance of two novel cancer-associated proteins in this disease.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Biomarkers, Tumor/analysis , Mass Spectrometry , Transcription Factors/analysis , Nuclear Proteins/analysis , Blotting, Western , Chromatography, Liquid , Proteomics , DNA-Binding Proteins/analysis
5.
Article in Chinese | WPRIM | ID: wpr-880076

ABSTRACT

OBJECTIVE@#To construct an acute myeloid leukemia cell line stably expressing CD123-CLL1 so as to provide an "in vitro" model for studying the role of CD123 and CLL-1 in leukemia and the treatment targeting CD123 and CLL-1.@*METHODS@#The recombinant plasmid of lentivirus was constructed by synthesizing CD123 and CLL-1 sequences and PCR homologous recombination. The lentivirus vector was packaged by three-plasmid packaging system. After collecting the supernatant of lentivirus, the virus titer was determined by quantitative PCR. K562 leukemia cells were collected and transtected with virus supernatant. Leukemia cell line stably expressing the target gene were screened by purinomycin. The expression levels of CD123 and CLL-1 were detected by RT-PCR and flow cytometry.@*RESULTS@#The lentiviral vector was successfully constructed, and identified by agarose gel electrophoresis and gene sequencing, then the virus titer of the supernatant was up to 5.81×10@*CONCLUSION@#Lentiviral vector expressing CD123-CLL1 has been successfully constructed, and K562 leukemia cell line stably expressing CD123 and CLL-1 has been successfully obtained.


Subject(s)
Cell Line, Tumor , Genetic Vectors , Humans , Interleukin-3 Receptor alpha Subunit , K562 Cells , Lentivirus/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Plasmids , Transfection
6.
Journal of Experimental Hematology ; (6): 1671-1675, 2021.
Article in Chinese | WPRIM | ID: wpr-922315

ABSTRACT

Chronic lymphocytic leukemia (CLL) patients usually show immune dysfunction, which often leads to autoimmune hemocytopenia. Immune thrombocytopenia (ITP) is one of the common complications. The pathogenesis of CLL-related ITP is complex and has not been fully elucidated. At present, the researches mainly focus on humoral immunity, cellular immunity and innate immune disorders. Recent studies suggest that genomic abnormalities and microRNAs are also involved in CLL-related ITP. Traditional ITP standard therapy has a poor effect on CLL-related ITP. Chemotherapy or monoclonal antibody therapy against the primary pathogenesis of CLL can effectively treat thrombocytopenia, and the emergence of new targeted drugs also provides new treatment options for the disease. In this paper, the progresses of CLL-related ITP pathogenesis, prognosis and treatment in recent years are reviewed.


Subject(s)
Antibodies, Monoclonal , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , MicroRNAs , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia
7.
Autops. Case Rep ; 11: e2020196, 2021. tab, graf
Article in English | LILACS | ID: biblio-1142407

ABSTRACT

B-cell prolymphocytic leukemia (B-PLL) is an extremely rare disease, accounting for approximately 1% of the lymphocytic leukemias. B-PLL generally occurs in older people. It is characterized by the presence of more than 55% prolymphocytes in the peripheral blood (PB), no or minimal lymphadenopathy, massive splenomegaly, and very high white blood cell counts. The prognosis of B-PLL patients is generally poor, with a median survival of 3 years, although a subset of patients may show a prolonged survival. Herein, we report a case of a 70-year-old male with weakness, generalized lymphadenopathy, and moderate splenomegaly at the initial presentation. Hematologic examination revealed lymphocytic leukocytosis, favoring a chronic lymphoproliferative disorder (CLPD). The key to decoding the precise CLPD was a combination of the clinical profile, morphologic findings on the peripheral blood and the bone marrow, immunophenotypic analysis, and cytogenetic study. The best diagnosis proffered was a de novo chronic lymphocytic leukemia/prolymphocytic leukemia. There was no prior history of lymphoproliferative disorder or lymphocytic leukocytosis. Discriminating this entity from other lymphoproliferative disorders is crucial as the treatment and prognosis are varied compared to the other lymphoproliferative disorders. The diagnostic conundrum encountered and the incredible utility of ancillary studies in such a scenario are highlighted in this study.


Subject(s)
Humans , Male , Aged , Leukemia, Lymphocytic, Chronic, B-Cell , Leukemia, Prolymphocytic , Leukemia, Lymphoid , Leukemia, Prolymphocytic, B-Cell , Rare Diseases , Lymphadenopathy
8.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(3): 261-268, July-Sept. 2020. tab
Article in English | LILACS | ID: biblio-1134048

ABSTRACT

ABSTRACT Chronic lymphocytic leukemia is the most common hematologic malignancy among adults in Western countries. Several studies show that somatic mutations in the TP53 gene are present in up to 50% of patients with relapsed or refractory chronic lymphocytic leukemia. This study aims to review and compare the methods used to detect somatic TP53 mutations and/or 17p deletions and analyze their importance in the chronic lymphocytic leukemia diagnosis and follow-up. In chronic lymphocytic leukemia patients with refractory or recurrent disease, the probability of clonal expansion of cells with the TP53 mutation and/or 17p deletion is very high. The studies assessed showed several methodologies able to detect these changes. For the 17p deletion, the chromosome G-banding (karyotype) and interphase fluorescence in situ hybridization are the most sensitive. For somatic mutations involving the TP53 gene, moderate or high-coverage read next-generation sequencing and Sanger sequencing are the most recommended ones. The TP53 gene mutations represent a strong adverse prognostic factor for patient survival and treatment resistance in chronic lymphocytic leukemia. Patients carrying low-proportion TP53 mutation (less than 20-25% of all alleles) remain a challenge to these tests. Thus, for any of the methods employed, it is essential that the laboratory conduct its analytical validation, documenting its accuracy, precision and sensitivity/limit of detection.


Subject(s)
Humans , Leukemia, Lymphocytic, Chronic, B-Cell , Genes, p53 , Chromosome Deletion , Mutation
9.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(3): 269-274, July-Sept. 2020. ilus
Article in English | LILACS | ID: biblio-1134046

ABSTRACT

ABSTRACT Recent advances in chronic lymphocytic leukemia (CLL) includes description of disease genomic landscape, inclusion of prognostic relevant genetic tests in CLL workflow and evaluation of minimal residual disease (MRD)1 in parallel with the increase availability of novel therapy agents.In this review, the theoretical and practical aspects of response assessment have been discussed. These are based on updated recommendations of the European Research Initiative on Chronic Lymphocytic Leukemia (ERIC) for genetic tests (TP53 mutation and IGHV status) and flow cytometry analysis for CLL. Methodological approaches and interpretation of results were also discussed.2,3


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Genes, p53 , Neoplasm, Residual , Flow Cytometry , Mutation
10.
An. bras. dermatol ; 95(3): 336-339, May-June 2020. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1130869

ABSTRACT

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.


Subject(s)
Humans , Male , Aged , Prostatic Neoplasms/complications , Skin Diseases/complications , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Adenocarcinoma/complications , Graves Disease/complications , Collagen Diseases/complications , Skin Diseases/pathology , Collagen , Collagen Diseases/pathology
11.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(2): 103-110, Apr.-June 2020. ilus
Article in English | LILACS | ID: biblio-1134022

ABSTRACT

ABSTRACT: The novel Coronavirus (CoVid-19) outbreak is now consider a world pandemic, affecting more than 1,300,000 people worldwide. Cancer patients are in risk for severe disease, including a higher risk of intensive care unit (ICU) admission, need for invasive ventilation or death. Management of patients with lymphoid malignancies can be challenging during the outbreak, due to need of multiple hospital visits and admissions, immunosuppression and need for chemotherapy, radiotherapy and stem cell transplantation. In this article, we will focus on the practical management of patients with lymphoid malignancies during the COVID-19 pandemic, focusing on minimizing the risk for patients.


Subject(s)
Leukemia, Lymphoid , Coronavirus , COVID-19 , Lymphoma , Hodgkin Disease , Leukemia, Lymphocytic, Chronic, B-Cell , Lymphoma, B-Cell , Lymphoma, T-Cell, Peripheral , Lymphoma, Mantle-Cell
12.
Article in Chinese | WPRIM | ID: wpr-829039

ABSTRACT

OBJECTIVE@#To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics.@*METHODS@#Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes.@*RESULTS@#The expression level of miR-181b in CLL patients was significantly lower than that in control group (P<0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P<0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P<0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P<0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging.@*CONCLUSION@#The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.


Subject(s)
Apoptosis Regulatory Proteins , Cell Proliferation , Humans , Leukemia, Lymphocytic, Chronic, B-Cell , Genetics , MicroRNAs , Prognosis
13.
Article in Chinese | WPRIM | ID: wpr-827198

ABSTRACT

OBJECTIVE@#To analyze the diagnostic value of multiple reverse transcription-polymerase chain reaction (RT-PCR) for detecting different fusion genes in children with primary acute lymphoblastic leukemia (ALL).@*METHODS@#The clinical data of 80 children with ALL treated in the 2 affiliated hospital of Xi'an Medical College from September 2012 to September 2017 were collected and retrospectively analyzed. Immunophenotype, chromosome karyotype and fusion gene were analyzed.@*RESULTS@#Immunophenotyping showed that there were 2 cases of mixed expression of myeloid + B system, 2 cases with pre- B expression, 58 cases with former B expression, 11 cases with CD13 combined with pre- B expression, 4 cases with CD5 combined with pre- B expression, and 3 cases with CD2 combined with pre- B expression. The results of chromosome karyotype analysis showed that among 72 cases of karyotype analysts 5 cases could not be analyzed, 27 cases were determined to be normal karyotype, 11 cases with abnormal karyotype and 29 cases without mitotic phase. Six fusion genes were expressed in 30 cases (37.50%) of 80 ALL children, including MLL/AF9, CBF/MYH 11, BCR/ABL, TLS/ERG, MLL/ENL and TEL/AML1. Among the 3 cases with MLL/AF9 fusion gene expression [t(9;11)], 2 cases showed a poor response to early treatment, but achieved complete remission after intensive chemotherapy, and 1 case accepted bone marrow transplantation; in 1 case with CBF/MYH 11 fusion gene expression, treatment was abandoned by family members, and 4 cases with BCR/ABL fusion gene expression [t (9;22) (q34; q11)] were all showed poor response to early treatment, and achieved complete remission after intensive chemotherapy. All the fusion genes were positive during remission, including 2 cases of bone marrow transplantation; 1 case with TLS/ERG fusion gene expression [t (16;21)] displayed poor response to early treatment, and completely remitted after intensive chemotherapy; 2 cases with MLL/ENL fusion gene expression [t (11;19)] recurred during chemotherapy; 19 cases with TEL/AML1 fusion gene expression [t (12;21)] also achieved complete remission. 4 cases achieved a partial remission.@*CONCLUSION@#Genotyping can make up for the insufficiency of MICM typing, and multiplex RT-PCR can be used to rapidly detect the fusion genes caused by chromosomal aberration in children with ALL.


Subject(s)
Child , Chromosome Aberrations , Humans , Leukemia, Lymphocytic, Chronic, B-Cell , Genetics , MicroRNAs , Genetics , Oncogene Proteins, Fusion , Retrospective Studies
14.
Journal of Experimental Hematology ; (6): 1419-1423, 2020.
Article in Chinese | WPRIM | ID: wpr-827101

ABSTRACT

Venetoclax is a selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2(BCL-2)and has great potential in treating a variety of hematological tumors. In recent years, domestic and foreign scholars have tried to use venetoclax singal or in combination with some drugs to treat the patients with hematological tumors, including elderly acute myeloid leukemia(AML)patients un suitable for intensive chemotherapy, relapsed or refractory chronic lymphocytic leukemia(CLL), Non-Hodgkin's lymphoma(NHL)and multiple myeloma(MM)patients, these studies have achieved good results.At the same time,some scholars found that the secondary drug-resistance occurred in some patients who continuous treated with Venetoclax, and explored the Venetoclax-resistant mechanism. In this review, the research advance of Venetoclax in hematological tumors and the mechanisms of drug resistance are summarized and discussed briefly.


Subject(s)
Aged , Antineoplastic Agents , Therapeutic Uses , Bridged Bicyclo Compounds, Heterocyclic , Therapeutic Uses , Hematologic Neoplasms , Humans , Leukemia, Lymphocytic, Chronic, B-Cell , Drug Therapy , Sulfonamides
15.
Autops. Case Rep ; 9(3): e2019090, July-Sept. 2019. ilus, graf
Article in English | LILACS | ID: biblio-1020995

ABSTRACT

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.


Subject(s)
Humans , Male , Middle Aged , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Non-Hodgkin , Leukemia, Lymphocytic, Chronic, B-Cell , Cytogenetics
16.
Salud(i)ciencia (Impresa) ; 23(4): 332-338, mar. 2019. tab, graf
Article in Spanish | LILACS, BINACIS | ID: biblio-1010189

ABSTRACT

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. The disease has\r\na highly variable clinical course, ranging from very indolent cases to patients with aggressive and rapidly\r\nprogressing outcome. Genetic studies are useful tools in analyzing this pathology, and have been incorporated in international risk classifications. The analysis of genomic rearrangements and the mutational status of immunoglobulin heavy chain variable have allowed risk groups of high prognostic value to be established. More recently, next generation sequencing studies have identified novel somatic mutations that could explain the wide clinical variability of this pathology. Among them, the analysis of NOTCH1 (neurogenic locus notch homolog protein 1) gene mutations are of interest, as deregulation is associated with tumorigenesis. NOTCH11 mutations are mostly located at exon 34 (80% of cases) and 3´UTR (untranslated region). They produce premature stop codons that produce a constitutively active and stable NOTCH1 protein. NOTCH1 mutations are associated with adverse prognosis and refractoriness to treatment. The aim of this study was to analyze NOTCH1 mutations in CLL patients by ASO-PCR and sequencing. Our results found 4.4% of cases with NOTCH1 mutated values concordant with international observations (5%-10%). Including them in the genetic status of CLL patients allows the characterization of risk groups, an aspect of great importance in clinical practice and therapeutic decisions, to be refined.


La leucemia linfocítica crónica (LLC) es la leucemia más frecuente en adultos de Occidente. Presenta\r\nun curso clínico altamente variable, con pacientes que requieren tratamiento inmediato y otros con un curso indolente de la enfermedad. Los estudios genéticos constituyen herramientas de suma utilidad en esta enfermedad, encontrándose incorporados a las clasificaciones de riesgo internacionales. El análisis de los rearreglos genómicos y del estado mutacional de los genes IGHV (immunoglobulin heavy chain variable region) ha hecho factible establecer grupos de riesgo de alto valor pronóstico. Más recientemente, estudios de secuenciación de última generación permitieron la detección de mutaciones\r\nsomáticas previamente desconocidas en esta afección, que podrían explicar la amplia variabilidad clínica\r\nobservada en la LLC. Entre ellas, resultan de interés las observadas en el gen NOTCH1 (neurogenic locus notch homolog protein 1), cuya desregulación se asocia con el desarrollo tumoral. Estas mutaciones se acumulan en mayor medida en el exón 34 (80% de los casos) y en la región 3´UTR (untraslated region), lo que genera codones de terminación prematuros que originan una proteína NOTCH1 constitutivamente activa y más estable, los cuales se asocian con pronóstico adverso y refractariedad al tratamiento. Nuestro objetivo fue evaluar mutaciones de NOTCH1 en nuestros pacientes mediante ASO-PCR y secuenciación. Se detectaron mutaciones en el 4.4% de los casos, valor concordante con los datos internacionales (5% a 10%). Su inclusión en la caracterización genética de los pacientes con LLC permitirá refinar la categorización de los grupos de riesgo, aspecto de suma importancia tanto en el seguimiento clínico como en la toma de decisiones terapéuticas.


Subject(s)
Humans , Leukemia, Lymphocytic, Chronic, B-Cell , Cytogenetics , Receptor, Notch1 , Mutation/genetics
18.
Journal of Experimental Hematology ; (6): 1395-1401, 2019.
Article in Chinese | WPRIM | ID: wpr-775708

ABSTRACT

OBJECTIVE@#To investigate effect and mechanism of miR-214 in fludarabine resistance of chronic lympho-cytic leukemia (CLL).@*METHODS@#A total of 10 patients with CLL resistante to fludarabine (Flu) and 10 healthy persons admitted to Hematology Department of our hospital in August 2014 - July 2018 were selected. Expression level of miR-214 in mononuclear cells in patients with CLL and healthy persons were determined by RT-PCR. Primary CLL cells from patients with CLL were divided into normal control group (control group), negative control group (miR-214-NC group) and viral transinfection group (miR-214-ASO group). After 24 h-transfection, CLL cells were cultured with different con-centration of Flu for 48 h, then the cell proliferation and apoptosis were detected, and the levels of down-stream genes and proteins releted with PTEN and PI3K/AKT signialing pathway were determined.@*RESULTS@#The expression level of miR-214 in mononuclear cells of CLL patients significantly increased in comparison with healthy persons(P<0.05); the expression level of miR-214 in miR-214-ASO group significantly decreased (P<0.05); Absorbance in control group at Flu concentration of 3, 10 and 30 μmol/L was significantly decreased (P<0.05). Apoptosis rate in miR-214-ASO group at Flu concentration of 10 mmol/L significantly increased (P<0.05). At Flu concentration of 10 mmol/L, mRNA levels PTEN and BAD in miR-214-ASO group significantly increased (P<0.05), but mRNA levels of MDM2 and NF-κB significantly decreased (P<0.05). At Flu concentration of 10 mmol/L, protein levels of PTEN and p-BAD in miR-214-ASO group significantly increased (P<0.05), but protein levels of MDM2 and NF-κB significantly decreased (P<0.05).@*CONCLUSION@#Inhibition of miR-214 can enhance the sensitivity of drug-resistant CLL cells to fludarabine, which may be raleted with the promotion of cell apotosis and regulation of down-stream molecules expression of PTEN/AKT signaling pathway.


Subject(s)
Apoptosis , Humans , Leukemia, Lymphocytic, Chronic, B-Cell , Drug Therapy , MicroRNAs , Phosphatidylinositol 3-Kinases , Vidarabine , Genetics , Therapeutic Uses
19.
Chinese Medical Journal ; (24): 525-533, 2019.
Article in English | WPRIM | ID: wpr-774810

ABSTRACT

BACKGROUND@#Serum antinuclear antibodies (ANAs) are positive in some patients with chronic lymphocytic leukemia (CLL), but the prognostic value of ANAs remains unknown. The aim of this study was to evaluate the role of ANAs as a prognostic factor in CLL.@*METHODS@#This study retrospectively analyzed clinical data from 216 newly diagnosed CLL subjects with ANAs test from 2007 to 2017. Multivariate Cox regression analyses were used to screen the independent prognostic factors related to time to first treatment (TTFT), progression free survival (PFS) and overall survival (OS). Receiver operator characteristic curves and area under the curve (AUC) were utilized to assess the predictive accuracy of ANAs together with other independent factors for OS.@*RESULTS@#The incidence of ANAs abnormality at diagnosis was 13.9%. ANAs positivity and TP53 disruption were independent prognostic indicators for OS. The AUC of positive ANAs together with TP53 disruption was 0.766 (95% confidence interval [CI]: 0.697-0.826), which was significantly larger than that of either TP53 disruption (AUC: 0.706, 95% CI: 0.634-0.772, P = 0.034) or positive ANAs (AUC: 0.595, 95% CI: 0.520-0.668, P < 0.001) in OS prediction. Besides, serum positive ANAs as one additional parameter to CLL-international prognostic index (IPI) obtained superior AUCs in predicting CLL OS than CLL-IPI alone.@*CONCLUSION@#This study identified ANAs as an independent prognostic factor for CLL, and further investigations are needed to validate this finding.


Subject(s)
ADP-ribosyl Cyclase 1 , Blood , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Antinuclear , Blood , Autoimmunity , Physiology , Female , Humans , Kaplan-Meier Estimate , Leukemia, Lymphocytic, Chronic, B-Cell , Blood , Mortality , Male , Middle Aged , Multivariate Analysis , Mutation , Genetics , Proportional Hazards Models , Retrospective Studies , Survival Analysis , Tumor Suppressor Protein p53 , Blood , Young Adult , ZAP-70 Protein-Tyrosine Kinase , Blood
20.
Chinese Medical Journal ; (24): 551-561, 2019.
Article in English | WPRIM | ID: wpr-774800

ABSTRACT

BACKGROUND@#Classification of the pulmonary neuroendocrine tumor (pNET) categories is a step-wise process identified by the presence of necrosis and number of mitoses per 2 mm. In neuroendocrine tumor pathology, Ki-67 was first described as a prognostic factor in the pancreas and incorporated into the grading system of digestive tract neuroendocrine neoplasms in the 2010 WHO classification. However, the significance of Ki-67 in pNETs was still a controversial issue. This study was to investigate the potentially diagnostic value of Ki-67 in pNETs.@*METHODS@#We retrieved 159 surgical specimens of pNETs, including 35 typical carcinoids (TCs), 2 atypical carcinoid (ACs), 28 large-cell neuroendocrine carcinomas (LCNECs), 94 small-cell lung cancers (SCLCs). Manual conventional method (MCM) and computer-assisted image analysis method (CIAM) were used to calculate the Ki-67 proliferative index. In CIAM, 6 equivalent fields (500 × 500 μm) at 10× magnification were manually annotated for digital image analysis.@*RESULTS@#The Ki-67 index among the 4 groups with ranges of 0.38% to 12.66% for TC, 4.34% to 29.48% for AC, 30.67% to 93.74% for LCNEC, and 40.71% to 96.87% for SCLC. The cutoff value of Ki-67 index to distinguish low grade with high grade was 30.07%. For the univariate survival analyses in pNETs, both the overall survival and progression-free survival correlated with Ki-67 index. In addition, the Ki-67 index performed by CIAM was proved to be of great positive correlation with MCM.@*CONCLUSIONS@#Ki-67 index counted by CIAM is a reliable method and can be a useful adjunct to classify the low- and high-grade NETs.


Subject(s)
Adult , Aged , Aged, 80 and over , Carcinoma, Neuroendocrine , Metabolism , Pathology , Female , Humans , Immunohistochemistry , Ki-67 Antigen , Metabolism , Leukemia, Lymphocytic, Chronic, B-Cell , Metabolism , Pathology , Male , Middle Aged , Neuroendocrine Tumors , Metabolism , Pathology , Prognosis , World Health Organization
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