Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

The molecular genetic characteristics of a family with rare -88 C>G (HBB: c.-138 C>G) β-thalassemia gene mutation were studied using cohort study. The cohort study was conducted from June to August 2022 by Prenatal Diagnosis Center of Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center. The phenotype and genotype were analyzed by hematological cytoanalyzer, automatic electrophoretic analysis system, and next-generation sequencing (NGS). And then, Sanger sequencing was used to verify the rare gene results. The results showed that the proband, her father, her uncle and her younger male cousin had discrete microcytosis (MCV 70.1 fl, 71.9 fl, 73.1 fl and 76.6 fl, respectively) and hypochromia (MCH 21.5 pg,22.0 pg,22.6 pg and 23.5 pg, respectively), elevated hemoglobin A2 level (5.3%, 5.4%, 5.4% and 5.5%, respectively), slightly elevated or normal fetal hemoglobin (Hb F), but no anemia. The proband was identified to have co-inherited ɑ-thalassemia (Hb Westmead gene heterozygous mutation, ɑ^wsɑ/ɑɑ) and β-thalassemia with a rare -88 C>G (HBB: c.-138 C>G) heterozygous mutation (β^{-88 C>G}/β^N). Her mother had the same α-thalassemia as the proband. Her father, her uncle and her younger male cousin had the same rare -88 C>G heterozygous mutations as the proband. While her grandmother and younger brother were not carrier of thalassemia. In conclusion, 4 cases of rare -88 C>G(HBB:c.-138 C>G) heterozygous mutation had been detected in a Chinese family. Carriers of this beta-thalassemia are clinically asymptomatic. This study enriches the knowledge of the thalassemia mutation spectrum in Chinese people and provides valuable information for genetic counseling, prenatal diagnosis, and prevention of thalassemia, providing a scientific basis for improving the quality of birth population and preventing birth defects.
Female ; Humans ; Male ; alpha-Thalassemia/genetics* ; beta-Globins/genetics* ; beta-Thalassemia/diagnosis* ; China ; Cohort Studies ; Genotype ; Molecular Biology ; Mutation

OBJECTIVE: To investigate the effect of monoammonium glycyrrhizinate on the stem cell-like characteristics, oxidative stress and mitochondrial function of acute promyelocytic leukemia cells NB4. METHODS: CCK-8 method was used to detect the viability of acute promyelocytic leukemia cells NB4, and the appropriate dose was screened; Cloning method was used to detect the proliferation rate of NB4 cell; Western blot was used to detect the expression of cell cycle-related protein; flow cytometry was used to detect cell apoptosis and sort NB4 stem cells positive (CD133⁺); Stem cell markers (Oct4, ABCG2, Dclk1) were detected by RT-PCR; ROS was detected by fluorescence; The kit was used to detect the level of oxidative stress markers (MDA); The flow cytometry was used to detect the change of mitochondrial membrane potential; Western blot was used to detect the expression of mitochondrial damage index-related proteins (Bax/BCL-2). RESULTS: Compared with the control group, if the concentration of MAG was less than 5 μmol/L, the cell NB4 viability showed no significant difference; if the concentration was higher than 5 μmol/L, the inhibitory effect on the growth of cell NB4 increased and showed significant difference (P<0.05), according to the results of CCK-8 experiment, four groups were set based on the concentration of MAG 0 μmol/L, MAG 5 μmol/L, MAG 10 μmol/L, and MAG 20 μmol/L; compared with the control group (MAG 0 μmol/L), the cells in MAG 5 μmol/L group showed no significant difference, while the proliferation rate, cyclin expression, mitochondrial membrane potential, stem cell CD133⁺ ratio, and marker mRNA level ( Oct4, ABCG2, Dclk1) of NB4 cell were significantly reduced (P<0.05); the apoptosis rate, reactive oxygen species, MDA content and Bax/BCL-2 expression of NB4 cell significantly increased (P<0.05). CONCLUSION Monoammonium glycyrrhizinate has a significant inhibitory effect on acute promyelocytic leukemia cells NB4, which may be related to the regulation of stem cell-like characteristics, oxidative stress and mitochondrial function.
Apoptosis ; Cell Line, Tumor ; Doublecortin-Like Kinases ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism* ; Leukemia, Promyelocytic, Acute ; Mitochondria ; Oxidative Stress ; Protein Serine-Threonine Kinases ; Stem Cells

OBJECTIVE: To explain the clinicobiological heterogeneity of NPM1 mutated (NPM1^mut) acute myeloid leukemia (AML) by analyzing the association between next-generation sequencing (NGS) profiles and MICM characteristics in patients with this AML subtype. METHODS: Data of 238 NPM1^mut patients with available NGS information on 112 genes related to blood disease was collected, and χ² test and nonparametric test were used to analyze the distribution association between NGS-detecting mutations and conventional MICM parameters. RESULTS: In entire NPM1^mut cohort, totaling 240 NPM1 mutation events were identified, of whom 10 (10/240, 4.2%) were missense mutations, which did not involve any W288 or W290 locus and were found exclusively in NPM1^mut/FLT3-ITD^- group. All but one of these missense mutations (9/10, 90%) were accompanied by AML subtype-defining recurrent cytogenetic or molecular abnormalities, of which 7 cases were in the low risk and 2 in the high risk. NPM1^mut occurred solely as an insertion/deletion (indel) type in the NPM1^mut/FLT3-ITD⁺ group. The incidence of favorable plus unfavorable karyotypes in NPM1^mut/FLT3-ITD^- group was higher than in NPM1^mut/FLT3-ITD⁺ group (6.4% vs. 0, P=0.031). The positive rates of CD34 and CD7 in NPM1^mut/FLT3-ITD⁺ group were significantly higher than in NPM1^mut/FLT3-ITD^- group (CD34: 47.9% vs. 20.6%, P<0.001; CD7: 61.5% vs. 29.9%, P<0.001). Logistic analysis showed that FLT3-ITD independently predicted for CD34⁺ and CD7⁺ [odds ratio (OR)=5.29, 95%CI: 2.64-10.60, P<0.001; OR=3.47, 95%CI: 1.79-6.73, P<0.001; respectively]. Ras-pathway mutations independently predicted for HLA-DR⁺ (OR=4.05, 95%CI: 1.70-9.63, P=0.002), and KRAS mutation for MPO^- (OR=0.18, 95%CI: 0.05-0.62, P=0.007). TET2/IDH1 mutations independently predicted for CD34^- and CD7^- (OR=0.26, 95%CI: 0.11-0.62, P=0.002; OR=0.30, 95%CI: 0.14-0.62, P=0.001; respectively), and MPO⁺ (OR=3.52, 95%CI: 1.48-8.38, P=0.004). DNMT3A-R882 independently predicted for CD7⁺ and HLA-DR⁺ (OR=3.59, 95%CI: 1.80-7.16, P<0.001; OR=13.41, 95%CI: 4.56-39.45, P<0.001; respectively), and DNMT3A mutation for MPO^-(OR=0.35, 95%CI: 1.48-8.38, P=0.004). CONCLUSION Co-existing FLT3-ITD in NPM1^mut AML independently predicts for CD34⁺ and CD7⁺, co-existing Ras-pathway mutation for HLA-DR⁺ and MPO^-, co-existing TET2/IDH1 mutation for CD34^-, CD7^-, and MPO⁺, and co-existing DNMT3A mutation for HLA-DR⁺, CD7⁺, and MPO^-, thereby providing a new mechanism explanation for the immunophenotypic heterogeneity of these AML patients.
High-Throughput Nucleotide Sequencing ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Nuclear Proteins/genetics* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics*

OBJECTIVE: To distinguish clinical features, safety and efficiency of endoscopic retrograde cholangiopancreatography (ERCP) in patients after bilioenteric anstomosis based on retrospectively analyzed clinical data and endoscopy procedures. METHODS: Data extracted from patients after bilioenteric anstomosis due to biliary disease treated with ERCP from January 2005 to December 2021 in the Department of Gastroenterology, Peking University Third Hospital were retrospectively analyzed. Clinical data and endoscopic pictures were reevaluated and analyzed. The patients were divided into three groups, including the patients with choledochoduodenostomy (CDD), Roux-en-Y hepaticojejunostomy (RYHJ) and Whipple. Differences between ERCP success and failure were conducted. RESULTS: In the study, 89 cases with 132 ERCP procedures were involved, 9-80 years old, median 57 years old, containing 4 CDD, 30 RYHJ, 54 Whipple and 1 bile duct ileocecal anastomosis patients; The time between ERCP and surgery were 30 (1-40), 2.75 (0.5-14), 2 (0.3-19), and 10 years, respectively; The time between surgery and symptom were 240 (3-360), 12 (1-156), 22 (0-216), and 60 months, respectively. Fifty percent of CDD could succeed only under local anaesthesia, RYHJ (96.7%) and Whipple (100.0%) needed under general anaesthesia (P < 0.001). Successful first entry rates of CDD, RYHJ and Whipple were 100.0%, 40.0% and 77.8%, respectively. After changing the endoscopy type, successful entry rate could increase to 43.3% of RYHJ and 83.3% of Whipple. The successful entry rate of different anastomotic methods was significant (P < 0.001). The cannulation success rates of CDD, RYHJ and Whipple were 100.0%, 53.8% and 86.7% respectively, with significant difference between the groups (P=0.031). ERCP success rates of CDD, RYHJ and Whipple were 100.0%, 33.3% and 78.8% respectively, with significant difference between the groups (P < 0.001). Complications were found in 23.9% (21/88) patients, including infection (14.8%), pancreatitis (9.2%), bleeding (3.4%), and perforation (2.3%) ranked by incidence. Causes of ERCP in post bilioenteric anstomosis were anastomotic stenosis (50.0%, benign 39.3%, malignant 10.7%), choledocholithiasis (37.5%) and reflux cholangitis (12.5%). Anastomotic method was the only predicting factor of ERCP success in patients after bilioenteric anstomosis (OR=7, 95%CI: 2.591-18.912, P < 0.001). CONCLUSION ERCP in post bilioenteric anstomosis patients with gastrointestinal reconstruction need general anaesthe-sia, with good safety and efficiency. The successful rate of RYHJ was significantly lower than Whipple. Anastomotic method was the only predicting factor of ERCP success.
Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Cholangiopancreatography, Endoscopic Retrograde/methods* ; Anastomosis, Roux-en-Y/methods* ; Retrospective Studies ; Intestine, Small ; Anastomosis, Surgical

Objective:To explore the clinical characteristics of pancreaticobiliary maljunction (PBM) and its disease spectrum, and to evaluate therapeutic endoscopic retrograde cholangiopancreatography (ERCP).Methods:Data of 52 PBM patients who received therapeutic ERCP procedures for abdominal pain, jaundice and fever in Department of Gastroenterology of Peking University Third Hospital from June 2006 to March 2021 were collected. The clinical characteristics, typing, the change of disease spectrum and ERCP procedures were analyzed.Results:Among 52 PBM patients, female was more common. Abdominal pain and jaundice were the most common clinical manifestations, among which 20 were type Ⅰ, 25 type Ⅱ and 7 type Ⅲ. Half patients had the choledochal cyst. The mean timespan from the first onset to the final diagnosis was 12.2 years. Twenty-four cases (46.2%) had changes in PBM disease spectrum. Among 69 ERCP procedures, 5 (7.2%) failed. Difficult cannulation rate was 34.6% (18/52), and 11 patients underwent advanced cannulation techniques, while it was 15.4% (657/4 275) in the conterpart non-PBM patients in the same period, with significant difference between them ( χ2=14.455, P<0.05). Multiple therapeutic ERCP techniques including endoscopic sphincterotomy, pancreatic stent placement, removal of stones from the duct were applied with the successful rate of 92.8% (64/69). The incidence of post-ERCP pancreatitis was 15.4% (8/52). Conclusion:The chief clinical problem may be changed over time in PBM patients. Although ERCP plays an important role in PBM and its disease spectrum, there may be a higher rate of difficult cannulation and postoperative complications.

OBJECTIVE: To the clinical characteristics and prognostic value of the patients with complete deletion of TET_JBP domain (ΔJBP) in TET2 acute myeloid leukemia (AML). METHODS: Next Generation Sequencing technology was used to determine the mutations of 34 AML-related genes (including TET2 gene). The I-TASSER tool was used to predict the tertiary structure of the full-length TET2 protein and TET_JBP structure deletion. RESULTS: Among 38 AML patients with TET2 mutations, 22(57.9%) showed truncation mutations, of which 16 (72.7%) produced TET2ΔJBP truncation mutants. Protein structure prediction showed that the deletion of TET_JBP domain lead to the significant changes of tertiary structure in TET2 protein. Compared with the patients in non-ΔJBP group, the age of patients in ΔJBP group were older (63 vs 54 years old, P=0.047), and the occurrence rate of CEBPA double mutation (CEBPA CONCLUSION AML patients with TET2ΔJBP truncation mutant shows lower CR rate, shorter EFS and OS after induction chemotherapy, which may be related to the poor prognosis, and co-mutation with CEBPA
DNA-Binding Proteins/genetics* ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Prognosis ; Proto-Oncogene Proteins/genetics* ; Remission Induction

OBJECTIVE: To analyze the influence of serum homocysteine (Hcy) levels to the prognosis of newly diagnosed multiple myeloma (MM) patients, and to explore related factors affecting the prognosis of the patients. METHODS: The clinical pathological data of 180 newly diagnosed MM patients treated in our hospital from March 2013 to February 2015 were collected, and the patients were divided into high and low Hcy groups based on the median Hcy. The survival curves of the patients in the two groups were drawn to compare the differences of the survival; univariate and multivariate survival analysis was used to observe the influence of serum cysteine to the prognosis of newly diagnosed MM patients; the clinicopathological data of the patients with high and low Hcy in the two groups was compared, Pearson test was used to further analyzes the relationship between Hcy and different factors, and explores the related factors of Hcy affecting the prognosis of the patients. RESULTS: The median survival times of patients in the high and low Hcy groups were 32 (5-59) and 41 (7-71) months, respectively. The 3-year survival rate of the patients in high Hcy group was significantly lower than those in low Hcy group, and the difference shows statistically significant (P<0.05). The results of univariate survival analysis showed that the OS of newly diagnosed MM patients whom with advanced age, high bone disease grade, high-level bone marrow plasma cell count, LDH, C-reactive protein, Cr, β CONCLUSION Serum Hcy level has a correlation trend with the survival of newly diagnosed MM, which is affected by factors such as Hb.
Bone Marrow Cells ; Homocysteine ; Humans ; Multiple Myeloma ; Prognosis ; Risk Factors

OBJECTIVE: To investigate the expression of CD56 in multiple myeloma (MM) cells and its relationship between extramedullary disease and extramedullary relapse. METHODS: Clinical data of 99 patients with MM treated in our hospital from January 2015 to December 2019 was retrospectively analyzed. The patients were divided into positive group and negative group according to the expression of CD56. The relationship between CD56 and multiple myeloma extramedullary disease, extramedullary relapse was analyzed. RESULTS: Among 99 newly diagnosed patients with MM, the positive rate of CD56 was 65%, and the incidence of extramedullary disease of patients in the CD56 positive group was lower than that in the CD56 negative group (17.19% vs 48.57%) (P<0.01). Meanwhile, the incidence of extramedullary relapse of patients in the CD56 positive group was lower than that in the CD56 negative group (1.56% vs 34.29%) (P<0.01). CONCLUSION CD56 is highly expressed in MM, and its low expression is associated with the occurrence of extramedullary disease and extramedullary relapse, which suggests that CD56 may be an important indicator for predicting the occurrence of extramedullary disease and extramedullary relapse.
CD56 Antigen ; Humans ; Multiple Myeloma ; Neoplasm Recurrence, Local ; Retrospective Studies

OBJECTIVE: To investigate the quantitative expression of immunophenotype of CD34 METHODS: Multi-parameter flow cytometry (FCM) was used to detect the proportion and mean fluorescence intensity (MFI) of each antigen of bone marrow CD34 RESULTS: Bone marrow blast cell proportion (P<0.01), RBC level (P<0.01), and Hb level (P<0.05) of high-risk MDS patients were higher, while EPO level (P<0.05) was lower than those of low-risk patients. The proportion of CD34 CONCLUSION The immunophenotype of CD34
Antigens, CD34 ; Bone Marrow ; Bone Marrow Cells ; Flow Cytometry ; Humans ; Immunophenotyping ; Myelodysplastic Syndromes