<b>OBJECTIVEb>To summarize the recent findings of dysregulation of signaling pathways and miRNAs in chronic lymphocytic leukemia (CLL).

<b>DATA SOURCESb>We searched PubMed database with the keywords "chronic lymphocytic leukemia", "signal pathway", or "miRNA" for relevant articles in recent years.

<b>STUDY SELECTIONb>Research articles and reviews about signaling pathways and miRNAs in CLL were chosen for review.

<b>RESULTSb>Dysregulation of signaling pathways, such as B cell receptor , toll-like receptor, PI3K, nuclear factor κB, notch signaling pathway, Wnt/Fzd signaling pathway, and Hedgehog and Janus kinases/signal transducers and activators of transcription signaling pathway, as the terminal events of the aberrant gene expression and the pro-survival effects of microenvironment, plays a crucial role in the process of CLL. miRNAs, a novel found noncoding RNA, which regulate gene expression at transcription or post-transcription level and correlate with pathogenesis of CLL provide us new avenues to better evaluating prognosis and therapy of it.

<b>CONCLUSIONb>Further investigation of the dysregulation of signaling pathways and miRNAs and their relationship may provide us a new prospective to understand the pathogenesis of CLL and may provide us new strategies to resolve the clinical nodi in treatment of CLL.

Animals ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs ; genetics ; Signal Transduction ; genetics ; physiology

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.
Apoptosis Regulatory Proteins ; Cell Proliferation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs ; Prognosis

MicroRNA (miRNA) is a small endogenous noncoding single-stranded RNA molecule with about 22 nucleotides, and the high conservation in a variety of species exists in most eukaryotes. miRNA can recognize and bind to the 3'untranslated region (3'UTR) of target mRNA via complementary base pairing, then degrading or inhibiting translation of the target mRNA. The miRNA participates in the growth and progression development of individual organism and of the disease by regulating the gene expression after transcription. Chronic lymphocytic leukemia (CLL) is a malignant proliferative disease of B lymphocytes with insidious onset, showing significant heterogeneity in the incidence of individual, disease progression, treatment response, clinical prognosis and so on. Now, more and more studies have shown that mutation or abnormal expression of miRNA are closely related to CLL occurrence, progression, prognosis and curative efficacy. Complex and diverse miRNA in CLL may play a role of oncogenes or tumor suppressor genes. In the near future, some miRNAs may even become fresh biomarkers or therapeutic targets of CLL. This review will focus on miRNA molecules related to the pathogenesis, prognosis and treatment of CLL.
Gene Expression Regulation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs

Objective:b> To analyze the clinicopathological characteristics of 11 cases of chronic lymphocytic leukemia (CLL) with t (14;19) (q32;q13) . Methods:b> The case data of 11 patients with CLL with t (14;19) (q32;q13) in the chromosome karyotype analysis results of the Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 2018, to July 30, 2022, were retrospectively analyzed. Results:b> In all 11 patients, t (14;19) (q32;q13) involved IGH::BCL3 gene rearrangement, and most of them were accompanied by +12 or complex karyotype. An immunophenotypic score of 4-5 was found in 7 patients and 3 in 4 cases. We demonstrated that CLLs with t (14;19) (q32;q13) had a mutational pattern with recurrent mutations in NOTCH1 (3/7), FBXW7 (3/7), and KMT2D (2/7). The very-high-risk, high-risk, intermediate-risk, and low-risk groups consisted of 1, 1, 6, and 3 cases, respectively. Two patients died, 8 survived, and 2 were lost in follow-up. Four patients had disease progression or relapse during treatment. The median time to the first therapy was 1 month. Conclusion:b> t (14;19) (q32;q13), involving IGH::BCL3 gene rearrangement, is a rare recurrent cytogenetic abnormality in CLL, which is associated with a poor prognosis.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics* ; Retrospective Studies ; Translocation, Genetic ; Chromosome Aberrations ; Karyotyping

There are great differences in the clinical process and prognosis of the chronic lymphocytic leukemia(CLL), the precise diagnosis is of importance to judge prognosis, guide therapy and research pathogenesis mechanism. The variable region mutation of immunoglobulin heavy chain is the most stable molecular index of disease prediction. The patients with sequence of IgHV somatic high mutation usually have a better prognosis and a more longer survival time than those without the mutation. The recent study has found that specific IgHV gene expression also can predict the disease outcome in some cases regardless of mutation. The clinical prognosis of CLL patients can be further stratified by specific IgHV gene expression. In this review, the progress in the research of the clinical significance of specific IgHV gene expression in the chronic lymphocytic leukemia is summarized.
Humans ; Immunoglobulin Variable Region ; genetics ; Immunoglobulin gamma-Chains ; genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; diagnosis ; genetics ; Mutation ; Prognosis

The variable heavy chain region (VH) genes of 3 untreated patients with B-cell chronic lymphocytic leukemia (B-CLL) were cloned and analyzed. The VH family used was VH3-11, VH3-72 and VH3-33. More than 2% difference from the corresponding germline gene was detected in all the 3 obtained potential functional genes (average 16.7). Mutation pattern analysis indicated evidence of antigen selective pressure observed in 1 of 3 cases. Our findings suggested that the tumor cells originate from post-GC cells.
Amino Acid Sequence ; Gene Rearrangement ; Humans ; Immunoglobulin Variable Region ; genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; Molecular Sequence Data ; Mutation

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.
Child ; Chromosome Aberrations ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs ; genetics ; Oncogene Proteins, Fusion ; Retrospective Studies

<b>OBJECTIVEb>To analyze the clinical and laboratory features of chronic lymphocytic leukemia (CLL).

<b>METHODSb>Retrospective investigation of 263 patients with CLL in our hospital between Feb. 2000 and Jan. 2007.

<b>RESULTSb>The median age was 60 years with male/female ratio of 2.17 : 1. Patients who were asymptomatic at diagnosis (35.4%) had low Rai grades. Fatigue and lymphadenopathy (54.8%) were the most common features at presentation. Infections, connective tissue diseases and secondary tumors frequently occurred in CLL. WBC counts were between (10 - 100) x 10(9)/L, with lymphocytes percentages more than 0.50 in 97.1% patients. Bone marrow was normal- to hyper-cellularity with lymphocytes percentages more than 0.300 in 99.4% patients. Diffuse infiltrations in bone marrow section were found in 72.2% patients. There were lower CD5 (85.1%) and higher CD25 (78.9%) positivities in the present series as compared with that in other reports. Hypogammaglobulinemia, especially hypo-IgM, usually occurred. Chromosome abnormality were rarely found by routine chromosome examination.

<b>CONCLUSIONSb>There were some clinical and laboratory characteristics different from that of abroad data. Further exploration of new markers is required for prognosis prediction and treatment choice.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; pathology ; Male ; Middle Aged ; Retrospective Studies

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.
Apoptosis ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; MicroRNAs ; Phosphatidylinositol 3-Kinases ; Vidarabine ; analogs & derivatives ; genetics ; therapeutic use

OBJECTIVE: To investigate the expression and clinical significance of T helper cell 9 (Th9) and its cytokine interleukin 9(IL-9) in peripheral blood of patients with chronic lymphocytic leukemia(CLL). METHODS: A total of 43 newly diagnosed patients with chronic lymphocytic leukemia in the First Affiliated Hospital of Xinjiang Medical University from June 2021 to June 2022 were selected as the case group. The patients were divided into Binet A group (13 cases), Binet B group (20 cases) and Binet C group (10 cases) by Binet staging system, and 20 healthy volunteers who underwent physical examinationin in our hospital in the same period served as control group. The proportion of Th9 cells in peripheral blood was detected by flow cytometry, the expression level of Th9 specific transcription factors PU.1 and IRF4 was detected by Western blot, and the expression level of serum cytokine IL-9 was detected by ELISA. The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in each group were compared, and the correlation between the proportion of Th9, IL-9 and clinicopathological indexes of CLL patients was analyzed. RESULTS: The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in CLL group were significantly higher than those in control group (P<0.05), the proportion of Th9 and the expression of IL-9 in Binet B and C group were higher than those in Binet A group (P<0.05), but there was no significant difference in the proportion of Th9 cells between Binet B group and C group (P>0.05). The expression of IL-9 in Binet C group was significantly higher than that in Binet B group (P<0.05) . The proportion of Th9 cells and IL-9 were highly expression in patients with β2 microglobulin abnormality, IGHV unmutation, P53 abnormality and hepatosplenic lymph node enlargement(P<0.05), but not related to age and sex (P>0.05). The results of Spearman correlation analysis showed that the proportion of Th9 in patients with CLL was negatively correlated with the lymphocytic account and lymphocyte proportion(r_s=-0.32，r_s=-0.34). The proportion of Th9 and IL-9 were positively correlated with Binet stage, Rai stage and CLL-IPI Scoring (r_s=0.79，r_s=0.54，r_s=0.58； r_s=0.72，r_s=0.63，r_s=0.45), but not with WBC, CD4⁺ T cells and CD8⁺T cells (P>0.05). The proportion of Th9 was positively correlated with IL-9 (r_s=0.53). CONCLUSION Th9 cells and IL-9 are abnormally highly expressed in CLL, which is related to the poor prognosis of CLL.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics* ; Interleukin-9 ; Clinical Relevance ; T-Lymphocytes, Helper-Inducer/pathology* ; Cytokines