Fatal Outcome ; Humans ; Inflammation ; immunology ; metabolism ; mortality ; Lymphoma, T-Cell ; immunology ; metabolism ; mortality ; Male ; Middle Aged

p63 is a recently described p53 homologue. It is involved in survival and differentiation of reserve/stem cells in epithelia. To obtain new insights into the role of p63 in malignant lymphomas (MLs), immunohistochemical staining for p63 and p53 was performed in 126 cases of MLs. p63 was expressed in 38 cases of MLs (30.2%) including 32/61 cases (52.5%) of diffuse large B-cell lymphoma (DLBCL), 1/8 cases (12.5%) of precursor T-lymphoblastic lymphoma (T-LBL), 4/14 cases (28.6%) of follicular lymphoma, 1/6 cases (16.7%) of T/NK cell lymphoma. Among p63 positive cases, p63 was strongly expressed in 15/32 cases of DLBCL and 1/1 case of T-LBL. p63 was not expressed in mantle cell lymphomas, peripheral T-cell lymphomas, marginal zone B-cell lymphomas, plasma cell myelomas and Hodgkin's lymphomas. p63 was coexpressed with p53 in 18/38 p63 positive cases in which only 4 cases were strongly coexpressed. All p63+/p53+ cases were DLBCL. p63 overexpression (above 30%) cases showed significant poor survival (p=0.0228) in DLBCL. However, there was no statistically significant correlation between p63 expression and IPI score on Multivariate analysis. We could speculate that p63 could act indirectly as an oncogene by inhibiting p53 functions. Stage of differentiation of neoplastic lymphocytes appears to have a correlation with p63 expression in MLs.
Gene Expression Profiling ; Humans ; Incidence ; Korea/epidemiology ; Lymphoma/*metabolism/*mortality ; Membrane Proteins/*metabolism ; Pseudolymphoma/*metabolism/*mortality ; Research Support, Non-U.S. Gov't ; Risk Assessment/*methods ; Risk Factors ; Survival Analysis ; Survival Rate ; Tumor Markers, Biological/*metabolism

To explore the Fas and mdr-1 expression and their correlation in multidrug resistance (MDR), Fas and mdr-1 expressions of bone marrow from 59 patients with newly diagnosed AL before therapy and after complete remission were detected by direct immunofluorescence with flow cytometry and semi-quantitative RT-PCR, respectively. The results showed that in newly diagnosed AL patients, Fas expression in AML was higher than in ALL (P < 0.05), mdr-1 expression in AML and ALL had no difference (P > 0.05), the expressions of Fas and mdr-1 had correlation (r = -0.282, P < 0.05) in AL; the results of simple-variable and multivariable COX survival factor model analysis suggested that Fas and mdr-1 expressions were prognostic factors for the effect of therapy and survival. Log rank test, comparing the groups of Fas(+) with Fas(-), mdr-1(+) with mdr-1(-), demonstrated that the CR rates and median remission time of every two groups had significant difference. It is concluded that in AL, Fas and mdr-1 expressions have high correlation with the effect of treatment, Fas expression probably is one of the favorable prognostic factors, mdr-1 is an unfavorable prognostic and less effective factor.
Adolescent ; Adult ; Aged ; Child ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Genes, MDR ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; metabolism ; mortality ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; metabolism ; mortality ; RNA, Messenger ; analysis ; fas Receptor ; analysis

OBJECTIVETo investigate the clinical significance of cyclin B1 expression in adult acute leukemia (AL) patients.

METHODSThe expression of cyclin B1 and p21 and their cell cycle distribution were measured by flow cytometry in 85 adult patients with de novo AL, 10 continuous complete remission (CCR) AL and 17 normal controls (NC). The mRNAs of cyclin B1, p21 cip1 and proliferation cell nuclear antigen (PCNA) in patients and NCs were measured with semi-quantity reverse transcription polymerase chain reaction (RT-PCR).

RESULTSCyclin B1 protein expression in de novo AL patients was significantly higher than that in NC (P < 0.001). It was higher in relapsed patients than in NC (P < 0.05) but was lower than in de novo AL (P < 0.01). There was no difference between the remission cases and NC (P = 0.21), and between CCR patients and NC (P > 0.05). The cyclin B1 overexpression ratio was higher than that of NC. A negative correlation between the expression levels of cyclin B1 and P21 was observed (r = -0.266, P < 0.05). The cyclin B1 protein expression level was positively correlated with its mRNA level. The expression of cyclin B1 was positively correlated with proliferation index (PI) levels, and with PCNA levels (rPI = 0.7314, rPCNA = 0.7152). Remission rate was higher in high cyclin B1 expression patients than in normal cyclin B1 expression patients (P < 0.01), so did the relapse rate (P < 0.01). Patients with higher cyclin B1 expression had higher survival rate.

CONCLUSIONCyclin B1 was overexpressed and abnormally distributed in cell cycle phases in de novo AL patients. Overexpression of cyclin B1 might be a favorable prognostic factor for patients with AL.

Adolescent ; Adult ; Cell Division ; Cyclin B ; analysis ; Cyclin B1 ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins ; analysis ; Flow Cytometry ; Humans ; Leukemia, Myeloid, Acute ; metabolism ; mortality ; therapy ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; mortality ; therapy ; Prognosis ; Recurrence ; Survival Rate

OBJECTIVETo analyze the isoforms of IKAROS in the bone marrow samples from children with acute B-lineage lymphoblastic leukemia (B-ALL) and to investigate the relationship between frequency of dominant-negative (DN) IKAROS isoforms and prognosis of B-ALL, and to preliminarily study the relevant mechanism.

METHODSA total of 137 children with newly diagnosed B-ALL, who sequentially entered the Department of Hematology and Oncology, Shanghai Children's Medical Center between January 2005 and September 2010, were included in the study. Nest-PCR, Sanger sequencing, and TA cloning were used to analyze the expression of IKAROS isoforms in these children. The relationship between frequency of DN IKAROS isoforms and prognosis of B-ALL was investigated.

RESULTSOf the 137 children with newly diagnosed B-ALL, 16 had expression of IK6, 14 had expression of IK4, and 2 had expression of IK7. There was significant difference in 2.5-year event-free survival between the cohorts of DN IKAROS and non-DN IKAROS (P=0.01). Analysis of the 10 paired of diagnosis/relapse samples from 10 patients with recurrence showed that 8 of 10 paired diagnosis and relapse samples had inconsistent expression of IKAROS isoforms. The rate of IK6 expression in relapse samples from 21 relapse ALL patients was significantly higher than in the 137 children with newly diagnosed ALL (62% vs 12%, P<0.01).

CONCLUSIONSExpression of DN IKAROS isoforms can be a poor prognostic factor in B-ALL and is closely associated with recurrence of B-ALL.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Ikaros Transcription Factor ; genetics ; Infant ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; mortality ; Prognosis ; Protein Isoforms ; genetics

OBJECTIVETo study the expression of β-integrin family members in children with T-cell acute lymphoblastic leukemia (T-ALL) and their significance.

METHODSQuantitative real-time PCR analyses were performed to assess the expression levels of β-integrin family members in bone marrow samples from 22 children with newly-diagnosed T-ALL and 21 controls (16 children with non-malignant hematologic disease and 5 healthy donors with bone marrow transplantation). Jurkat cells were treated with integrin inhibitor arginine-glycine-aspartate (Arg-Gly-Asp, RGD) peptide. The cell viability and apoptosis rate were determined by CCK8 assay and flow cytometry respectively.

RESULTSThe mRNA levels of integrins β, β, and βwere significantly lower in children with T-ALL than in controls (P<0.05). In T-ALL patients, high integrin βexpression was associated with lower white blood cell counts (<100×10/L), minimal residual disease (MRD) positivity, and day 33 bone marrow negative remission (P<0.05). In T-ALL patients, higher integrin βexpression was associated with relapse of T-ALL (P<0.05). Based on survival curve analysis, higher integrin βexpression was related to lower event-free survival and overall survival rates. RGD peptide treatment inhibited the proliferation of Jurkat cells and increased their apoptosis rate (P<0.05).

CONCLUSIONSβ-Integrin may play a role in the occurrence and development of T-ALL by affecting cell proliferation and apoptosis. The expression of integrin β5 is closely related to the risk of relapse of T-ALL. The expression of integrin β3 is closely related the treatment response and prognosis of T-ALL.

Child ; Child, Preschool ; Female ; Humans ; Integrin beta Chains ; genetics ; physiology ; Jurkat Cells ; Male ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; etiology ; metabolism ; mortality ; RNA, Messenger ; analysis

The aim of this study was to explore the clinical features and survival of adult patients with CD20 positive B-lineage acute lymphoblastic leukemia (B-ALL). The clinical manifestations, examination results, therapeutic effect and survival rate of 119 adult B-ALL patients diagnosed and treated in our hospital from May 2004 to January 2008 were analyzed retrospectively. The results showed that among 119 cases, CD20 positive B-ALL accounted for 40 cases (33.61%), CD20 negative B-ALL patents accounted for 79 cases (66.39), the percentage of male patients in CD20 positive and negative groups were 72.50% and 50.63%, the leukocyte counts at diagnosis in these two groups were (27.35+/-30.29)x10(9)/L and (0.11+/-81.72)x10(9)/L, respectively, there were significant differences (p<0.05), whereas the distribution of age, infiltration of liver, spleen, lymph nodes and central nervous system, the hemoglobin and platelet levels, the expression of myeloid lineage marker, the incidence of Ph chromosome, the ratio of hyperdiploid and normal karyotype, the complete remission rate within 4 weeks, induction death rate and relapse rate and so on in CD20 positive and negative groups showed no significant differences (p>0.05). The analysis of Kaplan-Meier curve on survival rate demonstrated that the median overall survival time and 3-year overall survival rate of adult B-ALL patients in CD20 positive and negative groups were 11.0 months and 12.0 months, 28% and 20% respectively, there were no statistical differences (p=0.832). It is concluded that the expression of CD20 in adult B-ALL appears to be associated with sex and leukocyte count, but not associated with other clinical features, which indicates no significant influence on the prognosis of patients.
Adolescent ; Adult ; Antigens, CD20 ; metabolism ; Female ; Humans ; Leukemia, B-Cell ; mortality ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; mortality ; Prognosis ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Young Adult

BACKGROUNDThe prognosis is poor for patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). The main reason for poor prognosis is multidrug resistance (MDR), for which the main phenotype is overexpression of P-glycoprotein (P-gp). This study explored the efficacy of ligustrazine as a salvage agent in patients with relapsed or refractory NHL, and the relationship to P-gp expression.

METHODSSixty patients were randomized to a reversal agent group, receiving ligustrazine plus chemotherapy, and a control group, receiving chemotherapy alone. Flow cytometry was performed to evaluate P-gp expression.

RESULTSIn the 56 patients we were able to evaluate, there was no statistically significant difference in progression-free survival (PFS) in the two groups (P = 0.0651), but the reversal agent group had a higher overall response rate (ORR) than did the control group (P = 0.048). Forty-one of 56 patients had P-gp(+) tumor cells. Among these patients, six of eighteen patients in the reversal agent group and in the control group had complete remission or complete remission/unconfirmed (CR+CRu) reflecting a significant advantage in the reversal agent group (P = 0.048). Patients with P-gp(+) tumor cells in the reversal agent group had a higher overall response rate (ORR) than did the control group (11/18 vs. 6/23, P = 0.024). Kaplan-Meier Survival curve and log-rank test demonstrated that patients with P-gp(+) tumor cells in the reversal agent group had longer progression-free survival than did the control group (P = 0.0464). A small number of patients who received ligustrazine had a decrease in blood pressure.

CONCLUSIONLigustrazine as a salvage agent in combination with chemotherapy can elevate response rate, prolong PFS with manageable toxicity, and correlate with P-gp expression in relapsed or refractory NHL.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Adult ; Aged ; Calcium Channel Blockers ; therapeutic use ; Female ; Humans ; Lymphoma, Non-Hodgkin ; drug therapy ; metabolism ; mortality ; Male ; Middle Aged ; Pyrazines ; therapeutic use ; Treatment Outcome ; Young Adult

This study was to investigate the predictive factors influencing prognosis of non-Hodgkin's lymphoma (NHL). The clinical data on 125 cases of NHL were analyzed retrospectively. The results indicated that in 125 cases, the incidence of B cell NHL (B-NHL) was 68%, T cell NHL (T-NHL) was 28%, and uncertained cases were 4%. B-NHL was with more bone marrow involvement, while T-NHL was associated with more presence of B symptom, increased lactate dehydrogenase (LDH), advanced clinical stage and higher International Prognostic Index (IPI) scores. For T-NHL and B-NHL, the 3-year overall survival (OS) rate was 41.07% and 71.64% respectively. Age, B symptom, LDH level, and clinical stage were associated with OS. Immunophenotyping was not identified as a significant prognostic factor. The incidence of born marrow involvement was 31.2%, mainly in B-NHL. The involvement manner had no relationships with age, B symptom, LDH level and T/B immunophenotyping. Diffuse bone marrow involvement was often linked with hepatosplenomegaly, and its OS was shorter than that focal manner. In conclusion, age, B symptom, LDH level and clinical stage affect NHL survival, while immunophenotyping was not an independent prognostic factor for NHL. The manner of bone marrow involvement helped to predict prognosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; pathology ; Child ; Child, Preschool ; China ; Female ; Humans ; Infant ; L-Lactate Dehydrogenase ; metabolism ; Lymphoma, B-Cell ; diagnosis ; Lymphoma, Non-Hodgkin ; diagnosis ; mortality ; pathology ; Lymphoma, T-Cell ; diagnosis ; enzymology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; Young Adult

BACKGROUND: It has been demonstrated that flow cytometric detection of minimal residual disease (MRD) has a prognostic significance in the treatment of patients with acute leukemia. We investigated the significance of flow cytometric MRD detection for the first time in Korea. METHODS: We analyzed the results of MRD detection in morphologically complete remission bone marrow aspirates from 89 patients with newly-diagnosed or relapsed acute leukemia, in which leukemic cells had cross-lineage antigen expression. Patients were grouped based on MRD frequencies: > or =1.0%, high MRD; <1.0%, low MRD. RESULTS: Forty-seven ALL patients consisted of 10 with high and 37 with low MRD levels. Patients with high MRD levels showed a tendency of more frequent relapse than those with low MRD levels (40.0% and 13.5%, respectively) (P=0.08). High MRD group showed a tendency of short relapse-free survival (RFS) and overall survival (OS), although the differences were not statistically significant. Forty-two AML patients consisted of 16 with high and 26 with low MRD levels. There were no correlations between the MRD levels and relapse rate, RFS or OS. AML patients with high MRD levels showed significantly higher rate of unfavorable cytogenetic risk categories and lower rate of favorable risk categories (P=0.03). CONCLUSIONS: MRD detection by flow cytometric assay of cross-lineage antigen expression would be useful in predicting treatment outcome in patients with ALL rather than AML. We expect that the establishment of the standardization of methods, time to test or antibody combination would be achieved through further trials in this country.
Acute Disease ; Adolescent ; Adult ; Aged ; Antigens/*metabolism ; Antigens, CD/metabolism ; Bone Marrow/metabolism ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; *Flow Cytometry ; Humans ; Infant ; Leukemia, Myeloid, Acute/*diagnosis/mortality/therapy ; Male ; Middle Aged ; Neoplasm, Residual/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/mortality/therapy ; Recurrence ; Survival Rate