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1.
Article in Chinese | WPRIM | ID: wpr-912534

ABSTRACT

Objective:To investigate the expression pattern of TCR variable region subfamily (Vβ and Vδ) in patients with mature T-cell lymphoma (TCL), and to compare the diagnostic value of TCRVβ and TCRVδ analysis in TCL.Methods:The TCRVβ flow cytometry kit was used to detect the expression of Vβ subtypes of αβT cell in 199 patients with αβ TCL and 398 patients with non-TCL, who hospitalized in Jiangsu Provincial People Hospital from 2011 to 2020. Among them, 185 cases of αβ TCL and 355 cases of non-TCL also underwent TCRβ and TCRγ gene rearrangement detection. The TCRVδ based 10-color protocol was used to detect the expression of Vδ subtypes in 24 cases of γδTCL, 10 cases of normal controls, and 15 cases with reactively higher CD4 and CD8 double-negative ratio from 2017 to 2020, and 24 cases of γδTCL and 15 cases with reactively higher CD4 and CD8 double-negative ratio underwent TCRβ, TCRγ and TCRδ gene rearrangement detection. The diagnostic performance and degree of coincidence for detecting malignant clonality were compared between TCRVβ and TCRVδ analysis and the TCR gene scanning method.Results:In the 199 cases of αβ TCL, 182 cases (91.5%) showed restricted expression or the sum of the positive percentages of the subgroups was less than 30% for the 24 TCRVβ subtypes. Among them, the subfamily members with the highest incidence of clonal T lymphocytes were TCRVβ13.2 (12.6%, 23/182) and TCRVβ3 (8.2%,15/182); the TCRVβ subtypes showed nonclonal results in 99.0% (394/398) of non-TCL. All 24 cases of γδTCL (100%) showed abnormal distribution patterns of Vδ1 and Vδ2, of which 19 cases showed restricted expression of Vδ1, and the remaining 5 cases had negative expression of either Vδ1 or Vδ2, and the positive rate of Vδ1 cells was significantly higher than that of Vδ2 cells (79.9%±10.8% vs 0.7%±0.3%, P<0.001). Among the normal control and cases with reactively higher CD4 and CD8 double-negative ratio, the positive rate of Vδ2 cells was significantly higher than that of Vδ1 cells (73.7%±6.7% vs 15.6%±4.2%, P<0.001), and all cases (25/25) showed a normal distribution pattern. In terms of the diagnostic performance of TCL, there was no significant difference of sensitivity and specificity between TCR variable region subfamily detection by flow cytometry and TCR gene scanning technology (the sensitivity was 92.4% and 91.4% respectively; the specificity was 99.0% and 95.9% respectively, P=0.065), and the coincidence rate of the two diagnostic methods is high (Kappa=0.809, P<0.001). Conclusion:Detection of TCR variable region subfamily by flow cytometry could quickly and effectively diagnose mature TCL.

2.
Journal of Experimental Hematology ; (6): 1746-1751, 2021.
Article in Chinese | WPRIM | ID: wpr-922328

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics of the patients with chronic myeloid leukemia (CML) discontinued tyrosine kinase inhibitors (TKI) therapy and the outcome of the patients.@*METHODS@#35 cases of CML patients experienced initiative discontinuation of TKI therapy in our hospital from June 1st 2015 to December 31th 2019 were retrospectively analyzed. The TFR of the patients and the factors affecting it were analyzed.@*RESULTS@#The median duration of TKI administration was 72 (range 35-173) months in the 35 patients. Among these patients, 8 had experienced TKI dose reduction or suspension. All the enrolled patients have achieved at least MMR. The median time for these patients achieving MMR was 15 (range 3-75) months after administration of TKI, and for MMR maintenance before TKI suspension was 55 (range 13-164) months. After TKI withdrawal the median follow up time was 20.3 (range 3-57.9) months, 22 out of 35 patients kept TFR, among them, 2 (5.71%) patients restarted TKI after 12 month suspension, and maintained MMR during suspension. 13 (37.1%)patients lost MMR, among them, 9 patients restarted TKI treatment, and 5 of them achieved MR4.0 after the median duration of 3(2-5) month. No patients were found to have disease progression. The estimated TFR rate was 57.8% and 51.8% at 12 and 24 months after discontinuation, respectively. Other clinical characteristic related to relapse were also analyzed, including the cumulative TKI administration duration, cumulative MMR duration, time to achieve MMR, median age at diagnosis, risk stratification by Sokal score, TKI dose reduction and discontinuation history, and second-generation TKI administration before stopping TKI, however, no statistical difference was found.@*CONCLUSION@#TKI discontinuation is practical for CML patients in our center.


Subject(s)
Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors , Recurrence , Retrospective Studies , Treatment Outcome
3.
Journal of Experimental Hematology ; (6): 1326-1331, 2020.
Article in Chinese | WPRIM | ID: wpr-827117

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics, laboratorial and bone marrow pathological features of primary thrombocytopenia (ET) patients with different mutations of CALR, JAK2 and MPL genes.@*METHODS@#The chinical data of 120 cases of ET in Jiangsu provincial people's hospital/ The First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2017 were collected and analyzed, including 76 cases with JAK2 gene mutation, 40 cases with CALR gene mutation, 2 cases with MPL gene mutations, 2 cases without gene mutation.@*RESULTS@#Among the ET patients, compared with the JAK2 gene mutation, CALR gene mutation showed statistically significant deareament of white blood cells and hemoglobin (P=0.001, P=0.01) and the male platelets in CALR group showed significant increament (P=0.04). Fourthermore, the average number of megakaryocytes and its cluster numbers in each hight power field of vision showed statistically significant decreament in CALR group as compared with JAK2 group (P=0.001, P=0.001), and thrombotic events in CALR group were signicantly lower than those in JAK2 group (7.5% vs 18.4%) (P=0.03).@*CONCLUSION@#Mutations of CALR, JAK2 have different clinical characteristics and blood pathological changes of Chinese ET patients, and their clinical significance is worth to explore.


Subject(s)
Bone Marrow , Calreticulin , Genetics , China , Humans , Janus Kinase 2 , Genetics , Male , Mutation , Receptors, Thrombopoietin , Genetics , Thrombocythemia, Essential
4.
Article in Chinese | WPRIM | ID: wpr-689545

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the clinical and laboratory features of acute myeloid leukemia (AML) with cuplike nuclei morphology.</p><p><b>METHODS</b>One hundred and seventy patients diagnosed with AML (M1andM2) between December 2009 and December 2016 were included in the study. Bone marrow smears were prepared for morphologic alanalysis, the immunophenotype was analyzed by flow cytometry and the RHG-banding was for conventional cytogenetic assay (CCA) ,gene mutation was detected by sequencing.</p><p><b>RESULTS</b>Among the 170 AMLpatients, 67 were diagnosed as M1 and 103 patients was diagnosed as M2, 43 patients(25.3%) defined as cuplike nuclei-positive, among them 38patients (88.4%) were M1 while only 5 patients (11.6%) were with M2(P<0.01). No significant value about sex(P> 0.05) between cuplike nuclei-positive and -negative group, while older patients were found in cuplike nuclei-positive group (P<0.05). Higher peroxydas (POX) ratio (P<0.05) and integration (P<0.05) were found in cuplike nuclei- positive group. Furthermore, the patients with cuplike nuclei-positive lack the expressions of CD34 (P<0.01) and HLA-DR(P<0.01) while no other immunophenotype markers were found. Among the 152 patients (89.4%) for genetic analysis ,83.8% karyotype of the cuplike nuclei-positive group were normal while only 54.8 of negative group was normal by CCA. Molecular biology analysis showed that the patients in cuplike nuclei-positive group have significantly highe rNMP1 (P<0.01) and FLT3(P<0.01) mutations as compared with the negative group. Furthermore, the relationship of the ratio o fcuplike nuclei and the type of gene mutations were investigated, and no significant associations were found. However, it was found that the patients with FLT3 mutation displayed more biological nuclear invagination than the patients with NPM1 mutations (P<0/01).</p><p><b>CONCLUSION</b>AML patients with positive cuplike nuclei have characteristic morphological changes, typical immunophenotype with HLA-DR- and CD34, normal karyotype accompanied by NPM1 and FLT3 mutations.</p>


Subject(s)
Cell Nucleus , Humans , Leukemia, Myeloid, Acute , Mutation , Nuclear Proteins , Prognosis , fms-Like Tyrosine Kinase 3
5.
Article in Chinese | WPRIM | ID: wpr-690980

ABSTRACT

<p><b>OBJECTIVE</b>The past studies found that the treatment of chronic myeloid leukemia (CML) with imatinib can induce the macrocytic anemia, moreover the incidence of anemia increases along with enhancement of imatinib concentration. This study was aimed to evaluate the potential relation of erythrocyte mean corpuscular volume (MCV) increase after the treatment with tyrosine kinase inhibitors (TKI) with the therapeutic response in patients with CML-chronic phase (CML-CP).</p><p><b>METHODS</b>The clinical and hematologic data including MCV, molecular and cytogenetic response of 119 patients with CML-CP were collected after treatment with TKIs, and the relation of MCV changes after treatment with the clinical characteristics and therapeutic efficacy for patients with CML-CP was analyzed.</p><p><b>RESULTS</b>The MCV in patients treated with TKIs for 12 months significantly increased as compared with that at initial diagnosis (P<0.05). The proportion of patients with increased MCV in group of complete cytogenetic response (CCyR) was significantly higher than that in group of non-CCyR (P<0.05). As compared with decreased MCV group, the patients in increased MCV group much more easily achieved CCyR after treatment for 6, 12 months (P<0.05, P<0.05) respectively, furthermore, much more easily maintained MMR (P<0.05).</p><p><b>CONCLUSION</b>The MCV as a parameter which is easily acquired may be a new marker for prodecting the therapeutic response of patients treated with TKIs.</p>


Subject(s)
Antineoplastic Agents , Erythrocyte Indices , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Protein Kinase Inhibitors , Treatment Outcome
6.
Journal of Leukemia & Lymphoma ; (12): 91-96,101, 2017.
Article in Chinese | WPRIM | ID: wpr-605854

ABSTRACT

Objective To explore the differences in clinical and laboratory parameters between elderly and non-elderly patients with acute lymphoblastic leukemia (ALL).Poor prognostic factors in elderly patients were explored to guide the individualized treatment.Methods Two hundred and seventy-nine ALL patients were divided into two groups:elderly group with their age more than 60 years (60-79 years) and nonelderly group with their age less than 60 years (14-59 years).The differences in clinical and laboratory parameters,abnormal molecular genetics on related genes,including IKZF1,PAX5,NOTCH1,PHF6,SH2B3,LEF1,and JAK1,as well as the correlations with treatment response and clinical outcome were compared between the two groups.Results Males accounted for a smaller part in elderly group [42.9 % (21/49) vs.61.7 % (142/230),P =0.015].The percentage of B cell lineage ALL (B-ALL),Philadelphia chromosome positive (Ph+) and CD33 positive rate were higher in elderly group compared with those in non-elderly group [87.8 % (43/49) vs.70.4 % (162/230),P=0.009;47.8 % (22/49) vs.27.4 % (58/230),P=0.007;56.8 % (21/49) vs.39.0 % (64/230),P =0.049,respectively].While both lymphodenopathy and total complete remission (CR) rate gained the upper hand in non-elderly group [38.9 % (81/230) vs.20.0 % (9/49),P=0.016;91.3 % (178/195) vs.68.3 % (28/41),P< 0.001,respectively].Moreover,elderly group had lower 3-month,6-month,12-month and 24-month overall survival (OS) rates (64.6 % vs.84.4 %,P=0.001;50.0 % vs.73.8 %,P=0.001;29.2 % vs.52.4 %,P=0.003;6.2 % vs.26.2 %,P=0.003,respectively) than those of non-elderly group.No significant differences in mutation rates of PAX5,NOTCH1,PHF6,SH2B3,LEF1 and JAK1 were found (all P > 0.05).Conclusions Compared with non-elderly ALL patients,elderly ones harbor their intrinsic characteristics which might give rise to inferior outcomes.As a consequence,more attention should be poured into treating this particular group of ALL patients to improve their prognosis.

7.
Article in Chinese | WPRIM | ID: wpr-311543

ABSTRACT

<p><b>OBJECTIVE</b>Cytokine receptor-like factor 2(CRLF2) plays an important role in the development of normal B lymphocytes, which can mediate early B cell proliferation and survival. The aim of this study was to investigate the mutations of CRLF2 and its clinical significance in adult patients with acute lymphoblastic leukemia(ALL).</p><p><b>METHODS</b>Exons of CRLF2 were amplified, then the DNA was purified and sequenced; the frequency, position, types and clinical significance of CRLF2 mutations were analyzed.</p><p><b>RESULTS</b>6 types of genetic alterations in CRLF2 were found, among them the R186S prompted better prognosis, while L86I, F232F and W255C associated with poor prognosis.</p><p><b>CONCLUSION</b>CRLF2 mutations may play an important role in the development and progressions of adult patients with ALL, and these genetic abnormalities may associate with clinical outcome.</p>

8.
Article in Chinese | WPRIM | ID: wpr-344171

ABSTRACT

<p><b>OBJECTIVE</b>To correlate the clinical features of patients with acute myeloid leukemia (AML) with mutations of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 genes as well as chromosomal aberrations.</p><p><b>METHODS</b>Somatic mutations of aforementioned genes in 412 newly diagnosed AML patients were detected with PCR and direct sequencing. All patients were also subjected to R-banding chromosomal analysis. The results were correlated with the clinical features and prognosis of the patients.</p><p><b>RESULTS</b>The mutation rates of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 were 9.0% (26/289), 19.1% (50/262), 18.9% (34/180), 3.4% (7/208), 6.6% (9/137) and 6.9% (4/58), respectively. Patients with poor prognosis based on genetic mutations had lower blood platelet count than those with intermediate and good prognosis (P=0.001 and P=0.001, respectively). None of the three groups attained median overall survival (OS) (P> 0.05). The complete remission (CR) was similar among the three groups (P> 0.05). For patients with different prognosis based on cytogenetic findings, white blood cell count in those with intermediate prognosis was higher than those with good and poor prognosis (P< 0.001 and P=0.004, respectively), while the blood platelet count of the intermediate group was higher than that of the group with good prognosis (P=0.018). No significant difference was found among the three groups in terms of hemoglobin level (P> 0.05). The group with poor prognosis has attained shorter OS compared with those with good and intermediate prognosis (P< 0.001 and P=0.003, respectively). However, the CR rate of the group with good prognosis was higher than that of the intermediate group (P=0.001). For the group with intermediate prognosis, presence of genetic mutations did not correlate with the clinic characteristics such as white blood cell count, blood platelet count, hemoglobin level, OS and CR rate (P> 0.05 for all comparisons).</p><p><b>CONCLUSION</b>Genetic mutations combined with cytogenetic analysis can facilitate the prognosis and personalized treatment for patients with AML.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Leukemia, Myeloid, Acute , Genetics , Mortality , Male , Middle Aged , Mutation , Prognosis , Young Adult
9.
Chinese Medical Journal ; (24): 1778-1783, 2016.
Article in English | WPRIM | ID: wpr-251304

ABSTRACT

<p><b>BACKGROUND</b>Recently, calreticulin (CALR) gene mutations have been identified in patients with essential thrombocythemia (ET). A high-frequency of ET cases without Janus kinase 2 (JAK2) mutations contain CALR mutations and exhibit clinical characteristics different from those with mutant JAK2. Thus, we investigated the frequency and clinical features of Chinese patients of Han ethnicity with CALR mutations in ET.</p><p><b>METHODS</b>We recruited 310 Chinese patients of Han ethnicity with ET to analyze states of CALR, JAK2V617F, and MPLW515 mutations by polymerase chain reaction and direct sequencing. We analyzed the relationship between the mutations and clinical features.</p><p><b>RESULTS</b>CALR, JAK2V617F, and MPLW515 mutations were detected in 30% (n = 92), 48% (n = 149), and 1% (n = 4) of patients with ET, respectively. The mutation types of CALR involved deletion and insertion of base pairs. Most of them were Type 1 (52-bp deletion) and Type 2 (5-bp insertion, TTGTC) mutations, leading to del367fs46 and ins385fs47, respectively. The three mutations were exclusive. Clinically, patients with mutated CALR had a lower hemoglobin level, lower white blood cell (WBC) count, and higher platelet count compared to those with mutated JAK2 (P < 0.05). Furthermore, a significant difference was found in WBCs between wild-type patients (triple negative for JAK2, MPL, and CALR mutations) and patients with JAK2 mutations. Patients with CALR mutations predominantly clustered into low or intermediate groups according to the International Prognostic Score of thrombosis for ET (P < 0.05).</p><p><b>CONCLUSIONS</b>CALR mutations were frequent in Chinese patients with ET, especially in those without JAK2 or MPL mutations. Compared with JAK2 mutant ET, CALR mutant ET showed a different clinical manifestation and an unfavorable prognosis. Thus, CALR is a potentially valuable diagnostic marker and therapeutic target in ET.</p>


Subject(s)
Adult , Aged , Aged, 80 and over , Asians , Genetics , Biomarkers , Calreticulin , Genetics , Female , Humans , Janus Kinase 2 , Genetics , Kaplan-Meier Estimate , Male , Middle Aged , Mutation , Receptors, Thrombopoietin , Genetics , Thrombocythemia, Essential , Genetics , Pathology , Thrombosis , Genetics , Young Adult
10.
Chinese Journal of Hematology ; (12): 902-905, 2015.
Article in Chinese | WPRIM | ID: wpr-296122

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the accuracy and consistency of the detection of BCR-ABL tyrosine kinase domain point mutation among different laboratories.</p><p><b>METHODS</b>Every one of 6 laboratories prepared 10 cDNA samples from tyrosine kinase inhibitors resistant BCR-ABL (P210 or P190) positive patients'bone marrow or peripheral blood. Each cDNA sample was divided into 6 aliquots and delivered to the laboratories. All 6 laboratories tested BCR-ABL point mutations of 60 samples according to their own protocols. Peking University People's Hospital analyzed the comparison results based on both the reports and sequencing chromatogram from all laboratories.</p><p><b>RESULTS</b>All laboratories reported the same nucleotide and corresponding amino acid mutations in 37 samples (61.7%). Of 60 samples, 53 had confirmed mutation types, and a total of 23 types were included; 1 had no mutation; mutation types of 6 samples could not be determined because of the big differences among chromatograms from different laboratories. Low percentages of mutants were significantly related to results inconsistency (P=0.008). Inconsistent result of one sample was caused by the unique chromatogram of the mutant L248V, and one by the non-coverage amplification of PCR product from different laboratories. Amplification was failed in 3 samples. Testing or sequencing mistakes occurred in 7 samples. The differences in the mutant percentages among laboratories were less than 20% in the 80.6% of samples with confirmed results. Low internal control gene copies (ABL<10 000) were significantly related to both failed amplification and big differences among chromatograms from different laboratories (P=0.005 and <0.001, respectively).</p><p><b>CONCLUSION</b>Problems in the clinical routine detection of BCR-ABL point mutation could be exposed and improvement could be achieved by sample exchange and comparison. Low percentage of mutant is the main reason which causes the discrepancy of BCR-ABL point mutation results among different laboratories.</p>


Subject(s)
Bone Marrow , DNA Mutational Analysis , Fusion Proteins, bcr-abl , Genetics , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Point Mutation , Polymerase Chain Reaction
11.
Article in Chinese | WPRIM | ID: wpr-357305

ABSTRACT

<p><b>BACKGROUD</b>F-Box and WD40 domain containing protein 7 gene (FBXW7) is part of the E3 ubiquitin ligase complex that controls the turnover of various proteins including NOTCH1, c-MYC and Cyclin E.</p><p><b>OBJECTIVE</b>To investigate the mutations of FBXW7 gene in adult T-cell acute lymphoblastic leukemia (T-ALL).</p><p><b>METHODS</b>Exon 5-12 of FBXW7 were amplified, cloned and sequenced in 54 adult T-ALL patients; the frequency, position and types of FBXW7 mutation were analyzed; the co-existing of mutations with NOTCH1 and their relevant prognostic significance were explored as well.</p><p><b>RESULTS</b>FBXW7 mutations were identified in 11.1% of adult T-ALL patients. A total of 4 types of point mutations (R465H, R465L, R479P and R505C) and 1 deletion/insertion mutation were observed, and all of them located in WD40 domain of FBXW7. In addition, co-existing mutations with NOTCH1 were identified in 83.3% of patients with FBXW7 mutation. Notably, the co-existed NOTCH1 mutations, including 3 point mutations (L1574P, L1596H and L1600P) and 2 deletion/insertion mutations located in HD domain. Furthermore, patients with FBXW7 mutation only had significantly longer overall survival compared with those without mutation (P=0.049).</p><p><b>CONCLUSION</b>FBXW7 mutations may play an important role in NOTCH1 mediated pathogenesis in T-ALL.</p>


Subject(s)
Adult , Cell Cycle Proteins , Exons , F-Box Proteins , F-Box-WD Repeat-Containing Protein 7 , Genes, myc , Humans , Mutation , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , Ubiquitin-Protein Ligases
12.
Article in Chinese | WPRIM | ID: wpr-357245

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the expression of BAG3 gene in acue myeloid leukemia (AML) and its prognostic value.</p><p><b>METHODS</b>Real-time quantitative RT-PCR was used to detect the expression of BAG3 mRNA in 88 previously untreated AML patients. The corelation of BAG3 expression level with clinical characteristics and known prognostic markers of AML was analyzed.</p><p><b>RESULTS</b>In 88 patients with AML, the expression of BAG3 mRNA in NPMI mutated AML patients was obviously lower than that in NPMI unmutated patients (P = 0.018). The expression level of BAG3 mRNA did not related to clinical parameters, such as age, sex, FAB subtype, WBC count, extra-modullary presentation, and to prognostic factors including cytogenetics, FLT3-ITD, c-kit and CEBPα mutation status (P > 0.05). The expression level of BAG3 had no obvious effect on complete remission (CR) of patients in first treatment. The expression level of BAG3 in non-M3 patients was higher than that in relapsed patients (P = 0.036). The expression level of BAG3 had no effect on overall survival (OS) of patients.</p><p><b>CONCLUSION</b>The expression level of BAG3 does not correlated with known-prognostic markers of AML, only the expression level of BAG3 in NPM1 mutated patients is lower than that in NPM1 unmutated patients. The expression level of BAG3 has no effect on OS of AML patients, the BAG3 can not be difined as a prognostic marker in AML.</p>


Subject(s)
Adaptor Proteins, Signal Transducing , Apoptosis Regulatory Proteins , Cytogenetics , Humans , Leukemia, Myeloid, Acute , Leukocyte Count , Mutation , Prognosis , Proto-Oncogene Proteins c-kit , RNA, Messenger , Real-Time Polymerase Chain Reaction , Remission Induction
13.
Article in Chinese | WPRIM | ID: wpr-349645

ABSTRACT

This study was aimed to enhance clinical understanding the effect of nilotinib on CML patients with V299L mutation who were resistant to imatinib. Bone marrow specimens from 2 cases of CML with V299L mutation were collected before and after the treatment with nilotinib. ABL mutation was detected by nested reverse transcription polymerase chain reaction (PCR) followed by direct sequencing. The clinical characteristics of the two cases were analyzed. The results showed that both cases were resistant to imatinib presented V299L mutation. Out of them 1 case achieved complete haematological response (CHR) after treatment with nilotinib for 6 months and another case abstained obvious molecular response after using nilotinib for 7 month. V299L mutation of both cases was turned into negative after the treatment with nilotinib. It is concluded that the nilotinib can safely and effectively override tyrosine kinase inhibitor (TKI) resistance mediated by the V299L mutation. The safety and efficacy of nilotinib for treatment of CML patients with TKI resistance and V299L mutation are satisfactory.


Subject(s)
Adult , Aged , Benzamides , Pharmacology , Drug Resistance, Neoplasm , Genetics , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Drug Therapy , Genetics , Male , Mutation , Piperazines , Pharmacology , Pyrimidines , Pharmacology , Therapeutic Uses
14.
Chinese Journal of Hematology ; (12): 134-137, 2014.
Article in Chinese | WPRIM | ID: wpr-295693

ABSTRACT

<p><b>OBJECTIVE</b>To validate the conversion factor (CF) for the conversion of BCR-ABL (P210) transcript levels to the international scale in chronic myeloid leukemia (CML).</p><p><b>METHODS</b>In 2012, the international reference laboratory in Adelaide, Australia (IMVS) sent two batches of RNA samples, 30 samples per batch, to Peking University People's Hospital (PKUPH). By comparing BCRABL (P210) transcript levels reported by the two laboratories, CF of PKUPH was calculated and validated by IMVS. In 2013, PKUPH prepared the exchange samples for validation of CF of 9 hospitals who have calculated CFs before. The fresh BCR-ABL (P210) (+) cells were serially diluted by BCR-ABL (P210) (-) cells to prepare 22 kinds of samples with different BCR-ABL transcript levels, each kind had 10 parallel samples. Trizol reagent was added in each tube. Ten hospitals tested BCR-ABL transcript levels of one set of 22 samples. Agreement between BCR-ABL transcript levels of each laboratory and PKUPH was assessed by the Bland-Altman method.</p><p><b>RESULTS</b>PKUPH successfully validated its CF with bias 1.1 fold and 95% limits of agreement between -4.7 and 4.9 fold. Of 9 hospitals whose validation performed by sample exchanges with PKUPH, 6 hospitals successfully validated their CF with bias ≤±1.4 fold and 95% limits of agreement within ±6 fold.</p><p><b>CONCLUSION</b>Validation of CF examined the stability of the detection of BCR-ABL (P210) transcript levels, which was necessary for the valid conversion of BCR-ABL (P210) transcript levels to the international scale in CML.</p>


Subject(s)
Fusion Proteins, bcr-abl , Genetics , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Genetics , Reverse Transcriptase Polymerase Chain Reaction , Reference Standards , Transcription, Genetic
15.
Journal of Experimental Hematology ; (6): 1531-1534, 2014.
Article in Chinese | WPRIM | ID: wpr-340464

ABSTRACT

This study was aimed to investigate the relationship between expression of CD200 antigen and clinical characteristics in AML patients and to analyse the value of CD200 in evaluation of AML prognosis. The CD200 and immunophenotypes were detected by flow cytometry, the chromosome karyotypes were determined by R banding, the FISH was used to measure the AML1/ETO, PML/RARa and inv(16), and PCR technique was used to detect the fusion genes AML1/ETO and PML/RARα. The results showed that the positive rate of CD200 antigen expression in 54 patients was 57.4% (31/54), the CD200 antigen expression between sex and age of patients was no significant different (P > 0.05). There was significant difference of CD200 expression between CD34 and CD117 (P < 0.05), but the difference of CD200 expression in chromosome karyotypes was no significant difference(P > 0.05). Moreover, there was significant difference of CD200 expression in CD34 and CD117 of CBF positive AML patients (P < 0.05). It is concluded that the CD200 antigen expression in AML may associate with a poor prognosis of patients.


Subject(s)
Antigens, CD , Allergy and Immunology , Chromosome Banding , Humans , Immunophenotyping , Karyotyping , Leukemia, Myeloid, Acute , Diagnosis , Genetics , Allergy and Immunology , Oncogene Proteins, Fusion , Prognosis
16.
Chinese Medical Journal ; (24): 4215-4219, 2014.
Article in English | WPRIM | ID: wpr-268391

ABSTRACT

<p><b>BACKGROUND</b>Spliceosome mutations have been recently identified and associated with hematological malignancies. SRSF2, one of components of the splicing machinery, has a high mutation frequency during chronic myelomonocytic leukemia, according to previous reports. However, the relevance of this finding in Chinese populations remains unknown.</p><p><b>METHODS</b>We recruited 50 Chinese patients with chronic myelomonocytic leukemia to analyze the state of SRSF2 and to assess the corresponding clinical features by polymerase chain reaction followed by direct sequencing.</p><p><b>RESULTS</b>Ten of 50 patients (20%) harbored SRSF2 mutations, including five P95R, two 95H, and three P95L point mutations. The patient group was older than the wild type group (P < 0.01). No significant statistical differences were observed with regard to the other clinical characteristics (sex, peripheral blood count, serum lactate dehydrogenase, karyotype, World Health Organization classification, etc.) between these two groups. Two of the patients showed an early evolution to acute myeloid leukemia.</p><p><b>CONCLUSIONS</b>SRSF2 mutations are frequent in chronic myelomonocytic leukemia patients, but show a relatively lower incidence in Chinese patients. Moreover, the mutation can be related to old age and an unfavorable prognosis. Our results provide valuable insights for the development of a diagnostic marker, or for the identification of a therapeutic target for chronic myelomonocytic leukemia.</p>


Subject(s)
Adult , Aged , Aged, 80 and over , DNA Mutational Analysis , Female , Genetic Predisposition to Disease , Genetics , Humans , Leukemia, Myelomonocytic, Chronic , Genetics , Male , Middle Aged , Mutation , Nuclear Proteins , Genetics , Ribonucleoproteins , Genetics , Serine-Arginine Splicing Factors
17.
Chinese Journal of Hematology ; (12): 708-712, 2014.
Article in Chinese | WPRIM | ID: wpr-242079

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the relationship of the mutational status of the ND4 gene and the clinical features of acute myelogenous leukemia (AML) patients with ND4 mutations.</p><p><b>METHODS</b>Using PCR combined with directly sequencing, we identified somatic mutations of ND4 in 121 primary AML patients to couple with their clinical features.</p><p><b>RESULTS</b>There were 58 male patients and 63 female patients (median age 49 years, 10-86 years). Eight of 121 patients (6.6%) with de novo AML were found harboring missense mutation of ND4 gene, including 3 patients with A131V (3/8, 37.5%), 2 patients with A404T (2/8, 25%), 1 patient with F149L (1/8, 12.5%), 1 patient with G242D (1/8, 12.5%) and 1 patient with Y409H (1/8, 12.5%), respectively. Patients with ND4 mutations were associated with good karyotype (P=0.049), regardless of gender, age, white blood cell, hemoglobin, platelet, blast cells of bone marrow or immunophenotype (P>0.05). There were no statistical significance in mutations of FLT3-ITD, NPM1, CEBPA, c-KIT and DNMT3A between patients with ND4 mutation and wild-type (wt) ND4 (P>0.05). The median overall survival of patients with ND4 mutations and wt ND4 were all not reached. The median relapse-free survival were not reached and 29(2-53) months, respectively (P>0.05). There was no significance in the ratio of CR and RR patients between wt ND4 and ND4 mutated groups (P>0.05).</p><p><b>CONCLUSION</b>It was concluded that novel ND4 mutations could be found in de novo AML patients, especially in patients with good karyotype. Thus, ND4 mutations might play an important role in AML prognosis. However, whether the mitochondria dysfunction contribute to leukemogenesis needs to be further investigated.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Leukemia, Myeloid, Acute , Drug Therapy , Genetics , Male , Middle Aged , Mutation , NADH Dehydrogenase , Genetics , Prognosis , Young Adult
18.
Chinese Journal of Hematology ; (12): 816-821, 2014.
Article in Chinese | WPRIM | ID: wpr-242052

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the impact of Fc gamma receptor IIIa (FcγR IIIa) polymorphisms on the efficacy of rituximab (RTX) combined chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>FcγRIIIa polymorphisms were analyzed by PCR in 122 patients and 100 healthy controls. All patients received 8(4-12) cycles of RTX combined chemotherapy.</p><p><b>RESULTS</b>78(63.93%) patients with F/F, 5(4.10%) with V/V, and 39(31.97%) with V/F were identified, which were not different compared to controls. Patients with different FcγRIIIa genotypes did not have any difference in terms of gender, age, molecular subtypes, lactate dehydrogenase (LDH) or international prognostic index (IPI). The overall response rate (ORR) was 89.35% with a complete response (CR) of 80.33% and a partial response (PR) of 9.02%. The ORR was 83.33%, 100.00% and 100.00% in F/F, V/V and V/F, respectively. A higher response rate was observed in V/V and V/F as compared with F/F (P<0.05). With a median follow-up of 35 months (range: 12-62 months), 46(37.71%) patients had relapsed and 40 (32.79%) cases progressed and ended in death. The 3-year progress-free survival (PFS) rate was 41.03%, 100.00%, 100.00% in F/F, V/V and V/F, respectively. The 3-year overall survival (OS) rate was 48.72%, 100.00% and 100.00% in patients with three genotypes. The PFS and OS rate were significantly higher in V/V and V/F as compared with F/F (P<0.05).</p><p><b>CONCLUSION</b>FcγR III a polymorphisms could predict response and prognosis of RTX combined chemotherapy for patients with DLBCL.</p>


Subject(s)
Antibodies, Monoclonal, Murine-Derived , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Asians , Genetics , Disease-Free Survival , GPI-Linked Proteins , Humans , Lymphoma, Large B-Cell, Diffuse , Drug Therapy , Genetics , Polymorphism, Genetic , Prognosis , Receptors, IgG , Genetics , Remission Induction , Rituximab
19.
Journal of Experimental Hematology ; (6): 1206-1211, 2014.
Article in Chinese | WPRIM | ID: wpr-302319

ABSTRACT

PAX5 is an important transcription factor of paired-box(PAX) family. The aim of this study was to investigate the mutations and expression of PAX5 and its clinical significance in adult patients with acute lymphoblastic leukemia (ALL). Reverse transcription polymerase chain reaction (RT-PCR) and genomic PCR were performed to detect the deletions of PAX5 and point mutations of PAX5 exon 2-10 in 101 cases of adult ALL and were confirmed by cloning and sequencing. In addition, quantitative PCR (qPCR) was performed to evaluate the expression of PAX5. Furthermore, the correlations of mutations and expression of PAX5 with clinical parameters were analyzed, and the prognostic significance was evaluated as well. The results showed that PAX5 mutations were observed in 8 of 101 (7.9%) patients with B-ALL. A total of 9 types of mutations were detected, including 4 types of deletions, 4 types of point mutations and 1 insertion mutation; percentage of patients with age ≥ 50 years was higher in PAX5 mutation group than in wide-type group (62.5% vs 21.5%,P = 0.031) . The statistical differences were observed in B-cell subtype, initial platelet count and immunophenotypes between high and low expression of PAX5 (P < 0.05) . In addition, patients with high expression of PAX5 had higher first complete remission rate (86.7% vs 62.5%, P = 0.030) and 6-month overall survival rate (75.0% vs 50.0%, P = 0.034) compared with patients with low expression of PAX5. It is concluded that deletion/insertion/point mutations and aberrant expression of PAX5 can be observed in adult patients with B-ALL. Mutations and aberrant expression of PAX5 correlated with clinical parameters and have important clinical significance.


Subject(s)
Adult , Exons , Gene Expression Regulation, Leukemic , Humans , Mutation , PAX5 Transcription Factor , Genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Genetics , Prognosis , Sequence Deletion
20.
Journal of Experimental Hematology ; (6): 1212-1216, 2014.
Article in Chinese | WPRIM | ID: wpr-302318

ABSTRACT

Lymphoid enhancer factor 1 (LEF1) is a key transcription factor in Wingless-type (Wnt) pathway. The present study was aimed to explore the genetic mutation and expression of LEF1, and their clinical significance in adult patients with acute lymphocytic leukemia (ALL). Genomic DNA was amplified and sequenced to detect the mutation of LEF1 in 131 newly diagnosed adult patients with ALL. Quantitative PCR (qPCR) was performed to detect the expression of LEF1. Moreover, the correlations between mutations and expression of LEF1 with clinical characteristics were analyzed. The results showed that the frequency of LEF1 mutation in adult ALL was 3.1% (4/131) and all of them were point mutations located in exon 2 and 3; the median white blood cell count and median percentage of blasts at diagnosis were significantly higher in LEF1 high expression group than in low expression group (70.6 × 10⁹/L vs 26.2 × 10⁹/L)(P = 0.010); (81.0% vs 57.0%) (P = 0.014); in addition, the percentage of patients with Philadelphia chromosome positive and patients in high-risk group significantly increased in LEF1 high expression group compared with that in low expression group (66.7% vs 36.5%) (P = 0.038); (79.2% vs 56.2%) (P = 0.044). It is concluded that high expression of LEF1 may play an important role on development of adult ALL.


Subject(s)
Adult , Exons , Gene Expression Regulation, Leukemic , Humans , Lymphoid Enhancer-Binding Factor 1 , Genetics , Mutation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Genetics
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