ABSTRACT
OBJECTIVE@#To study the prognostic value of LPCAT1 in acute myeloid leukemia (AML).@*METHODS@#TaqMan-based reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect relative expression of LPCAT1 in 214 newly diagnosed adult AML patients and 24 normal controls. Survival functions were estimated using the Kaplan-Meier method and were compared by the Log-rank test. A Cox proportional hazard regression model was used to identify prognostic factors.@*RESULTS@#The expression level of LPCAT1 in adult AML was 34.37%(1.83%-392.63%), which was significantly lower than 92.81%(2.60%-325.84%) of normal controls (P<0.001). The prognostic significance of LPCAT1 was evaluated in 171 non-acute promyelocytic leukemia patients with complete clinical information and prognostic data. Survival analysis showed that the expression level of LPCAT1 had no significant effect on the prognosis of the whole cohort. However, in AML patients with FAB subtype M2 (AML-M2), the 2-year relapse-free survival (RFS) rate of patients with low LPCAT1 expression was 35.4%(95%CI: 0.107-0.601), which was significantly lower than 79.2%(95%CI: 0.627-0.957) of patients with high LPCAT1 expression (P=0.012). Multivariate analysis showed that low expression of LPCAT1 was an independent risk factor for RFS of AML-M2 patients (HR=0.355, 95%CI: 0.126-0.966, P=0.049).@*CONCLUSION@#In adult AML patients LPCAT1 shows low expression. Low LPCAT1 expression is an independent risk factor for RFS in M2-AML patients.
Subject(s)
Humans , Adult , Prognosis , Leukemia, Myeloid, Acute/metabolism , Survival Analysis , Proportional Hazards Models , Risk Factors , 1-Acylglycerophosphocholine O-AcyltransferaseABSTRACT
OBJECTIVE@#To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies.@*METHODS@#The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated.@*RESULTS@#A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the β2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027).@*CONCLUSION@#The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.
Subject(s)
Humans , Middle Aged , Aged , Aged, 80 and over , Multiple Myeloma/complications , Leukemia, Plasma Cell , Retrospective Studies , Esophageal Neoplasms/complications , Esophageal Squamous Cell Carcinoma/complications , Prognosis , Neoplasms, Second PrimaryABSTRACT
OBJECTIVE@#To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients.@*METHODS@#Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH).@*RESULTS@#Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression.@*CONCLUSION@#There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.
Subject(s)
Humans , Chromosome Aberrations , In Situ Hybridization, Fluorescence , Multiple Myeloma/genetics , MutationABSTRACT
OBJECTIVE@#To investigate the expression and clinical significance of serum protein ROCK2 in patients with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The patients were divided into cGVHD group and control group (without cGVHD). The expression levels of serum protein ROCK2 were detected by ELISA in patients with or without cGVHD after allo-HSCT.@*RESULTS@#The expression level of ROCK2 in serum of cGVHD patients was significantly higher than those in control group, moreover, the expression level of ROCK2 in severe cGVHD group was significant higher than that in moderate and mild cGVHD group (P<0.001). The expression level of ROCK2 was significantly decreased in the serum of cGVHD patients after treatment(P<0.01); the expression level of ROCK2 was significantly higher in the serum of cGVHD patients with lung as the target organ(P<0.01). The median survival time of patients with severe cGVHD were significantly shorter than that of patients with mild and moderate cGVHD(P<0.05).@*CONCLUSION@#ROCK2 shows certain reference value in the evaluation of severity and prognosis of cGVHD, and may be a new target for the treatment of cGVHD.
Subject(s)
Humans , Blood Proteins , Chronic Disease , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , rho-Associated KinasesABSTRACT
OBJECTIVE@#To analyze the clinical characteristics of patients with POEMS syndrome and explore its effective treatment strategies.@*METHODS@#The clinical data of 75 patients with POEMS syndrome treated in The First Affiliated Hospital of Zhengzhou University from June 2012 to June 2018 were collected and retrospectively analyzed. The clinical characteristics, treatment regimes and outcomes of the patients were summarized.@*RESULTS@#The median age of 75 diagnosed patients was 50 (30-81) years old and 100% (75/75) of the patients were accompanied with peripheral neuropathy, 77.3% (58/75) with organ enlargement, 82.7% (62/75) with endocrine abnormality, 93.3% (70/75) with monoclonal plasma cell diseases and 64.0% (48/75) with skin changes. Among the 75 patients, 5 cases gave up treatment, while the others showed varying degrees of improvement after treatment. The hematological complete remission (CR@*CONCLUSION@#The clinical manifestations of POEMS syndrome are complex and diverse, the clinicians therefore should be vigilant to reduce the misdiagnosis and missed diagnosis. Bortezomib or Lenalidomide can be recommended as the first-line medicines and autologous HSCT should be considered for appropriate patients.
Subject(s)
Aged , Aged, 80 and over , Humans , Middle Aged , Hematopoietic Stem Cell Transplantation , Lenalidomide , POEMS Syndrome/therapy , Retrospective Studies , Transplantation, AutologousABSTRACT
OBJECTIVE@#To explore the clinical characteristics and therapeutic efficacy of patient with adult acute lymphoblastic leukemia(ALL).@*METHODS@#Seventy-seven ALL patients diagnosed in the first affiliated hospital of Zhengzhou University from 2018 to 2019 were selected. The immunotyping, fusion gene and gene mutation were detected by flow cytometry, real-time quantitative polymerase chain reaction (RT-PCR) and next generation sequencing (NGS).@*RESULTS@#Among 77 patients with ALL, 66 were B-ALL, 9 were T-ALL. CD7 and cCD3 were the most valuable for the diagnosis of T-ALL, CD19 and cCD79a were the most valuable for the diagnosis of B-ALL, and CD58, CD123 were highly expressed in B-ALL. Three fusion genes: BCR-ABL (20.8%), MLL-AF4 (5.19%) and E2A-PBX1 (2.60%) were detected by RT-PCR and 10 mutant genes were detected by NGS (the total detection rate was 33.47%). The highest mutation rates were IL-7R (6 cases), NOTCH1 (6 cases), TP53 (5 cases) and FLT-3 (4 cases). Patients with IL-7R, NOTCH1 and TP53 mutations showed poor response to induction chemotherapy.@*CONCLUSION@#The CD123, IL-7R, NOTCH1 and TP53 may be risk factors for prognosis, however, the increase of case number and prolonging of follow-up time are needed to further confirm.
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OBJECTIVE@#To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS).@*METHODS@#The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (<60 years old) were compared.@*RESULTS@#The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ=7.180, P=0.007) and (20.0% vs 6.7%) ( χ=8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ=16.653, P=0.000) and (23.6% vs 8.7%)(χ=9.041, P=0.003) respectively.@*CONCLUSION@#The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.
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OBJECTIVE@#To investigate the expression of CD123 in patients with acute myeloid leukemia (AML) and its relationship between clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis.@*METHODS@#365 patients with newly diagnosed AML (except M3) treated in the First Affiliated Hospital of Zhengzhou University were enrolled and retrospective analysis, and multi-parameter flow cytometry was performed to detect the expression of CD123 in myeloid leukemia cell population. CD123≥20% was defined as positive. Clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis of CD123@*RESULTS@#The positive rate of CD123 in 365 newly diagnosed AML patients was 38.9%. Compared with the CD123@*CONCLUSION@#CD123 positive indicates that AML patients have higher tumor burden and are more difficult to reach remission. It is an independent risk factor for OS and EFS in patients with normal karyotype and intermediate risk, which is important to evaluate the prognosis of patients with AML without specific prognostic marker.
Subject(s)
Humans , Interleukin-3 Receptor alpha Subunit , Karyotype , Leukemia, Myeloid, Acute/genetics , Mutation , Patients , Prognosis , Retrospective StudiesABSTRACT
OBJECTIVE@#To investigate the IL-7R gene mutation and clinical features of adult patients with acute lymphoblastic leukemia (ALL).@*METHODS@#One hundred sixty-four cases of newly treated adults with ALL from May 2016 to December 2018 were selected. Targeted and specific next-generation sequencing technology was used to detected a total of 16 types of Ph-like ALL mutations, which include IL-7R mutation, and the cilinical features, rate, types and sites of IL-7R were analyzed.@*RESULTS@#IL-7R mutation was determined in 10 cases of 164 adult patients with ALL and the total mutation frequency was 13 times (6.1%). Out of 10 cases 5 cases were male (50%), 5 cases were female (50%). 6 cases of B-ALL ( 60% ) and 4 cases of T-ALL (40%). The mutation site of all cases was located at exon 6, among which 6 cases had replacement mutations, 3 cases had deletion mutations and 4 cases had insertion mutations. In addition, 1 triple and 1 double mutation of IL-7R were found. Besides, six mutation sites were newly identified, including: c.720_724del, c.723_726del, c.721_722insAGTG, c.727_728insTAACGGCCCCCTGCT, c.727_728insATGCAGGGAGCGAA and c.728_729insAAGTGTCA.@*CONCLUSION@#Six novel mutation sites and a poor manifestation of IL-7R have been explored in this research. Thus more samples are required to study the effects of IL-7R mutation on ALL treatment.
Subject(s)
Adult , Female , Humans , Male , Interleukin-7 Receptor alpha Subunit , Genetics , Mutation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Signal TransductionABSTRACT
OBJECTIVE@#To investigate the clinical features, accompanying gene mutation characteristics and prognostic factors of adult patients with acute myeloid leukemia with mutated NPM1 (NPM1AML).@*METHODS@#Seventy-three patients with newly diagnosed adult NPM1AML were selected. The mutations of 22 genes were detected by second generation sequencing and 43 fusion genes of AML were detected by real-time fluorescent quantitative PCR. The Kaplan-Meier survival curve and Cox multivariate regression analysis were used to study the prognostic factors.@*RESULTS@#A total of 74 NPM1 site mutations were detected in 73 patients with NPM1AML. The incidence rates were 92.0% L287fs, 2.7% Q289fs and W288fs, 1.4% L258fs and Q289H, among which 1 patient had 2 NPM1 mutations; the different mutation sites had no effect on the prognosis of NPM1AML. The median value of NPM1 variant allele frequency (VAF) was 35.4% (1.8%-56.6%). Based on the uppermost quartile of 38.4%, the patients were classified as NPM1 VAF>38.4% (NPM1AML) and NPM1 VAF≤38.4% (NPM1AML). Compared with NPM1AML, the early mortality rate was statistically significantly higher (33.3% vs 7.3%, P38.4% was an independent prognostic factor for EFS (HR=3.1, 95% CI 1.6-6.4, P<0.01) and OS (HR=3.0, 95% CI 1.4-6.2, P<0.01).@*CONCLUSION@#The NPM1 gene mutation in AML patients often is accompanied by other gene mutations, while the coexistence of fusion genes is rare; high NPM1 mutant allele burden is an independent prognostic factor for adult AML patients with mutated NPM1.
Subject(s)
Humans , Alleles , Leukemia, Myeloid, Acute , Genetics , Mutation , Nuclear Proteins , Genetics , Prognosis , fms-Like Tyrosine Kinase 3ABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of CC-chemokine receptor 7(CCR7) in patients with multiple myeloma(MM) and its correlation with clinical features of MM.</p><p><b>METHODS</b>The level of CCR7 expression in bone marrow samples from 53 newly diagnosed MM patients was detected by flow cytometry(FCM). Statistical methods were used to analyze the correlation between CCR7 expression and clinical features, such as sex, age, M protein, peripheral blood cell count, biochemical indicators, plasma cell ratio of bone marrow, immunophenotype, osteopathy and extramedullary disease.</p><p><b>RESULTS</b>The plasma cells in 24 out of 53 cases(45.28%) expressed CCR7. The rate of extramedullary disease in CCR7 positive group was significantly higher than that in CCR7 negative group (29.17% vs 3.45%)(P<0.05).</p><p><b>CONCLUSION</b>The expression of CCR7 in patients with MM is high, moreover this high expression correlates with extramedullary disease, thus CCR7 can be used as an effective indicator for prediction of extramedullary disease.</p>
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<p><b>OBJECTIVE</b>To analyze the kinase mutation ratio, related factors, effectiveness and safety of the second generation drugs for imatinib-resistant patients with chronic myeloid leukemia(CML).</p><p><b>METHODS</b>COX proportional hazard regression model was used for unvariate and multvariate analysis of various factors affecting the kinase mutation and for evaluating the effectiveness and safety of second generation tyrosine kinase inhibitor(TKI).</p><p><b>RESULTS</b>13 kinds of mutation were detected in 19 out of 42 cases for 22 times, including 4 times of F359V, 3 times of E255K, 2 time for F359C, F317L, T315I, Y253H, 1 time for D256R, C250R, D276G, F486S, M244V, Y256H and G250E, 3 cases with mixed mutations. The main adverse effects of patients receiving nilotinib were skin rash and fluid retention, while that for patients receiving dasatinib were eyelid edema and elevated bilirubin.</p><p><b>CONCLUSION</b>The WBC count, spleen enlargement degree, chromosome karyotypes, disease staging, drug used before treatment and time of acheiving CCyR are the related factors of the kinase mutations, but the patients receiving the second generation TKI can survive well.</p>
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<p><b>OBJECTIVE</b>To explore the effect of heat shock protein 90(HSP90) inhibitor 17-DMAG, an inhibitor specific for heat shock protein 90, on the proliferation and apoptosis of acute lymphocytic leukemia cell lines Jurkat.</p><p><b>METHODS</b>Jurkat cells were collected, then were treated with 17-DMAG. The expression of HSP90 was examined by semi-quantitative RT-PCR analysis, the effect of 17-DMAG on cell proliferation were detected by using WST, and cell apoptosis were detected by using flow cytometry with Annexin V/PI double stenining.</p><p><b>RESULTS</b>After Jurkat cells were treated with different concentrations of 17-DMAG for 48 hours, the HSP90 mRNA expression decreased significantly in dose dependent manner (r=0.9530, P<0.01). The ICwas 3.17 mmol/L when the Jurkat cells were treated with 17-DMAG for 48 h; after treating Jurkat cell with 17-DMAG, the cell proliferation was inhibited(r=0.9903, P< 0.01), the cell apoptosis was increased in dose dependent manner (r=0.9876, P<0.01).</p><p><b>CONCLUSION</b>17-DMAG can inhibit the Jurkat cell proliferation and induce the Jurkat cell apoptosis.</p>
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<p><b>OBJECTIVE</b>To investigate the role of HSP90 in proliferation and apoptosis of leukemia cells K562 through detecting the effect of HSP90 inhibitors 17-[2-(Dimethylamino) ethyl] amino-17-desmethoxygeldanamycin(17-DMAG) on leukemia K562 cell lines.</p><p><b>METHODS</b>The K562 cells were treated with HSP90 inhibitors 17-DMAG, the semi-quantitative PCR was used to detect HSP90 gene expression, the WST was used to detect the effect 17-DMAG on cell proliferation as well as Annexin V flow cytometry was used to detect the cell apoptosis.</p><p><b>RESULTS</b>After 17-DMAG treated the K562 cells in different stage, the K562 cell growth was obviously inhibited with time dependent (48 h)(r=0.9918) and dose dependent(3.2 µmol/L) manners (r=0.9999) (P<0.01); after the K562 cells in different stage were treated with different concentrations of 17-DMAG, the K562 cells showed significant apoptosis and with dosage-dependent mauner (r=0.9903)(P<0.01); HSP90 mRNA expression decreased significantly after K562 cells were treated with different concentrations of 17-DMAG for 48 hours. 17-DAMG down-regulated the HSP90 mRNA expression in dosage-dependent mauner as well(r=0.9227) (P<0.01).</p><p><b>CONCLUSION</b>HSP90 inhibitor 17-DMAG can inhibit the proliferation of K562 cells and induce their apoptosis. This study result provides laboratory basis for the treatment of leukemia patients with 17-DMAG.</p>
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<p><b>OBJECTIVE</b>To investigate the clinical efficacy of low-dose decitabine combined with CAG regimen in patients with myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB) through retrospective analysis.</p><p><b>METHODS</b>Thirty-six patients with MDS-RAEB who ever received low-dose decitabine combined with CAG regimen were enrolled into decitabine + CAG group and 40 patients with MDS-RAEB treated by decitabine alone in our center were enolled into the control group. The clinical characteristics, efficacy and adverse reactions (AE) were compared between the 2 groups.</p><p><b>RESULTS</b>Compared with the control group, the overall response rate (ORR) [complete remission (CR)+partial remission (PR) + hematologic improvement (HI) rate] of the decitabine+CAG group was higher (83.3% vs 62.5%)(P=0.043), and the AEs were not significantly increased. Cytopenia grade ≥3 and infection after treatment were the most prevalent AEs, which occurred in the early stage (within the first 2 cycles) and gradually decreased later. Other non-hematologic AEs were infrequent.</p><p><b>CONCLUSION</b>Low-dose decitabine combined with CAG regimen has better clinical efficacy for patients with MDS-RAEB than that of decitabine alone. It is worthy to be applied in clinic, especially for these patients who are not ineligible for hematopoietic stem cell transplantation.</p>
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<p><b>OBJECTIVE</b>To evaluate the clinical characteristics of multiple myeloma (MM) combined with renal amyloidosis and its curative efficacy and prognosis.</p><p><b>METHODS</b>The clinical data of 22 cases of newly diagnosed multiple myeloma combined with renal amyloidosis treated in our hospital from November 2011 to July 2015 were analyzed retrospectively.</p><p><b>RESULTS</b>According to Intenational Staging System (ISS), among above-menthioned 22 patients the ISS II accounted for 77.2% (17/22), ISS III accounted for 22.8% (5/22). The patients with renal impairment accounted for 36.4% (8/22), with anemia 40.9% (9/22), with serum album < 35 g/L 86.4% (19/22), with urinary protein positive 100% (22/22). The evaluation of the curative efficacy of the 22 cases was as follows: CR 13.6% (3/22); VGPR 4.5% (1/22); PR 22.8% (5/22); SD 45.5% (10/22); PD 13.6% (3/22). Out of 9 patients with effective treatment, 3 cases (3/9, 33.3%) achieved "improved" in renal amyloidosis, 4 cases (4/9, 44.5%) achieved stable in renal amyloidosis, 2 cases (2/9, 2%) achieved "worsened" in renal amyloidosis. Among 17 cases who were followed up, 7 cases died, 10 cases survived, the average duration of follow-up for these cases was 11 (1-37) months, the median overall survival (OS) time was 19 (95% CI 9.2-28.8) months.</p><p><b>CONCLUSION</b>MM with renal amyloidosis is rare, refractory and has a poor prognosis. Whether there is impairment of kidney function or not, renal amyloidosis shall be taken into consideration if the MM patients got massive proteinuria especially nephritic syndrome. Bortezomib may improve the curative efficacy.</p>
Subject(s)
Humans , Amyloidosis , Diagnosis , Pathology , Therapeutics , Bortezomib , Therapeutic Uses , Kidney Diseases , Diagnosis , Pathology , Therapeutics , Multiple Myeloma , Diagnosis , Pathology , Therapeutics , Prognosis , Proteinuria , Diagnosis , Retrospective Studies , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To explore the expression of CC-chemokine Receptor 7 (CCR7) in adult acute leukemia patients, and to analyze the relationship of CCR7 expression with the clinical characteristics of patients.</p><p><b>METHODS</b>The expression of CCR7 in bone marrow samples from adult acute leukemia patients were detected by flow cytometry (FCM), the relationship of CCR7 expression with the clinical characteristics of patients such as sex, age, WBC count, blast cell ratio, CD56 expression, molecular biology, cell genetics, risk stratification, extramedullary infiltration was analyzed.</p><p><b>RESULTS</b>The expression rate of CCR7 in adult ALL and AML patients was 36.8% and 9.6%, respectively, and the expression level of CCR7 in ALL patients was higher than that in AML patients (P < 0.05). The extramedullary infiltration rate was 100% and 41.7 % for CCR7 positive and negative groups of ALL, respectively (P < 0.05). While the mean fluorescence intensity (MFI) in extramedullary infiltration group of ALL was higher than that in none-extramedullary infiltration group of ALL (50.00 ± 10.42 vs 18.14 ± 1.39), respectively (P < 0.05).</p><p><b>CONCLUSION</b>CCR7 is higher expressed in adult acute leukemia cells, moreover its expression rate in ALL is higher than that in AML, and the expression of CCR7 is related with extramedullary infiltration in ALL.</p>
Subject(s)
Adult , Humans , Bone Marrow , Metabolism , Flow Cytometry , Leukemia, Myeloid, Acute , Genetics , Metabolism , Leukocyte Count , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Genetics , Metabolism , Receptors, CCR7 , Genetics , MetabolismABSTRACT
The purpose of this study was to investigate the immunophenotyping characteristics of adult acute lymphoblastic leukemia (ALL) patients in groups of different ages. Immunophenotyping was performed in 260 ALL patients by flow cytometry using a panel of monoclonal antibodies and CD45/SSC gating. The results indicated that (1) all the 82 cases of T-cell acute lymphoblastic leukemia (T-ALL) expressed CD7 (100%) while the positive rate of CD2 remarkably decreased with aging. The positive rate of CD2 in patients aged 14 to 18 years (adolescents) was 91.67%, which is significantly higher than that in cases aged 19 to 35 years (young adults) and > 35 years (older adults) (65.71% and 43.48% respectively, p < 0.05); the positive rate of CD34 and HLA-DR increased with aging, there was significant difference of the HLA-DR expression between the older adults group (39.13%) and the other two groups (4.17% in adolescents and 11.43% in young adults respectively (p < 0.05). Moreover, there were significant differences of the myeloid antigen (MyAg) and CD13 expression between the older adults and younger adults (p < 0.05). (2) As to adult B-cell acute lymphoblastic leukemia (B-ALL), the positive rates of CD19 and HLA-DR in 178 cases were 100%; the positive rate of CD33 in young adults was significant higher than that in adolescents (p < 0.05), the differences of the other marker expressions failed to reach statistical significance in adult B-ALL patients. It is concluded that the immunophenotypes of adult T-ALL are evidently heterogeneous in different ages, and expression with more aberrant phenotypes indicates poor prognostic significance in patients older than 35 years. There is no significant association of immunophenotypes with ages among different age groups of adult B-ALL.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Age Factors , Antigens, CD , Allergy and Immunology , Antigens, CD19 , Allergy and Immunology , Antigens, CD34 , Allergy and Immunology , Antigens, Differentiation, Myelomonocytic , Allergy and Immunology , CD13 Antigens , Allergy and Immunology , CD2 Antigens , Allergy and Immunology , Immunophenotyping , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Allergy and Immunology , Sialic Acid Binding Ig-like Lectin 3ABSTRACT
This study was purposed to investigate the inhibition of hTERT antisense oligodeoxynucleotide (ASODN) on the proliferation and telomerase activity in HL-60 cells and to explore the relativity between the telomerase activity and the expression of hTERT gene in HL-60 cells. After treated by hTERT ASODN the expression of hTERT was detected by RT-PCR, the morphological changes of HL-60 cells was observed with inverted microscopy, the cell proliferation was measured by MTT method, and the telomerase activity was determined with TRAP-ELISA and TRAP-PAGE. The results showed that after sealing hTERT gene with ASODN for 72 hours, the expression of hTERT gene was significantly inhibited, the cell growth was repressed and the ability of proliferation decreased, and the effect was specific in sequence and dependent in dose and time. OD(450-690) values were 2.648 +/- 0.42, 1.504 +/- 0.47, 1.223 +/- 0.39, 0.944 +/- 0.16 respectively, as the cells were treated with 0, 10, 20, 30 micromol/L ASODN for 72 hours. The difference was significant as compared 10, 20, 30 micromol/L groups with 0 micromol/L ASODN group respectively (P < 0.05), but the difference was no significant when compared 20 micromol/L SODN group (2.376 +/- 0.65) with untreated group (2.648 +/- 0.42) (P > 0.05). TRAP-PAGE detection revealed that comparing ASODN groups with SODN groups the telomerase image bands were decreased and least was found in groups of 30 +/- mol/L. It is concluded that the hTERT ASODN may inhibit the proliferation and down-regulate the telomerase activity in HL-60 cells by sealing the expression of hTERT gene.
Subject(s)
Humans , Cell Proliferation , HL-60 Cells , Oligonucleotides, Antisense , Genetics , Telomerase , Genetics , Metabolism , Pharmacology , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To evaluate cord blood stem cell transplantation (CBT) in the treatment of X-linked agammaglobulinemia, and observe the courses of the hematopoietic and immune reconstitution.</p><p><b>METHODS</b>A 14-year-old male patient with agammaglobulinemia received CBT from a 1/6 HLA-mismatched unrelated cord blood. The conditioning regimen was Bu/Cy/anti-CD3 antibody. CsA was given together with MMF and MTX for prophylaxis of GVHD. The patient received 0.42 x 10(8) nucleated cells/kg, containing 0.35 x 10(6) CD34(+) cells/kg.</p><p><b>RESULTS</b>The recipient showed hematopoietic reconstitution on day 30 post-transplantation when ANC was 0.5 x 10(9)/L and BPC 20 x 10(9)/L. Sex chromosome analysis showed engraftment (donor 46, XX/recipient 46, XY = 4:1) on day 45. The recipient's blood group changed from AB to O, IgG from 1.1 g/L to 3.5 g/L, sex chromosome from 46, XY to full 46, XX, and mature B cells in peripheral blood from 0 to 5% on day 100, indicating immune reconstitution. At the last follow-up of 360 days, the patient without acute or chronic GVHD showed normal hemogram and myelogram, IgG 13.5 g/L and 10% mature B cells in peripheral blood, indicating the hematopoiesis and immune persistent reconstitution. No acute or chronic GVHD was developed.</p><p><b>CONCLUSION</b>This is the first case report of successful treatment of X-linked agammaglobulinemia by HLA-mismatched unrelated CBT.</p>