OBJECTIVE: To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis. METHODS: A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared. RESULTS: The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×10⁹/L, among which 15 cases (68.18%) were >10×10⁹/L, and the median count of platelet (PLT) was 24(4-55)×10⁹/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively. CONCLUSION Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.
Middle Aged ; Humans ; Male ; Female ; Aged ; Leukemia, Myelomonocytic, Acute ; Retrospective Studies ; Leukemia, Myeloid, Acute/diagnosis* ; Prognosis ; Mutation ; Receptors, Colony-Stimulating Factor/genetics*

OBJECTIVE: To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABL^p190/210/230. METHODS: A new dPCR system for detecting BCR-ABL^p190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared. RESULTS: Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal. CONCLUSIONS This new dPCR detection system can be applied to the detection of BCR-ABL^p190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.
Humans ; Fusion Proteins, bcr-abl/genetics* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis* ; Polymerase Chain Reaction ; Drug-Related Side Effects and Adverse Reactions ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVES: To study the clinical and prognostic significance of the preferentially expressed antigen of melanoma (PRAME) gene in the absence of specific fusion gene expression in children with B-lineage acute lymphoblastic leukemia (B-ALL). METHODS: A total of 167 children newly diagnosed with B-ALL were enrolled, among whom 70 were positive for the PRAME gene and 97 were negative. None of the children were positive for MLL-r, BCR/ABL, E2A/PBX1, or ETV6/RUNX1. The PRAME positive and negative groups were analyzed in terms of clinical features, prognosis, and related prognostic factors. RESULTS: Compared with the PRAME negative group, the PRAME positive group had a significantly higher proportion of children with the liver extending >6 cm below the costal margin (P<0.05). There was a significant reduction in the PRAME copy number after induction chemotherapy (P<0.05). In the minimal residual disease (MRD) positive group after induction chemotherapy, the PRAME copy number was not correlated with the MRD level (P>0.05). In the MRD negative group, there was also no correlation between them (P>0.05). The PRAME positive group had a significantly higher 4-year event-free survival rate than the PRAME negative group (87.5%±4.6% vs 73.5%±4.6%, P<0.05), while there was no significant difference between the two groups in the 4-year overall survival rate (88.0%±4.4% vs 85.3%±3.8%, P>0.05). The Cox proportional-hazards regression model analysis showed that positive PRAME expression was a protective factor for event-free survival rate in children with B-ALL (P<0.05). CONCLUSIONS Although the PRAME gene cannot be monitored as MRD, overexpression of PRAME suggests a good prognosis in B-ALL.
Acute Disease ; Antigens, Neoplasm/therapeutic use* ; Child ; Humans ; Neoplasm, Residual/diagnosis* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis

OBJECTIVE: To explore the clinical-biological characteristics and prognosis of pediatric pro-B cell acute lymphoblastic leukemia (pro-B-ALL). METHODS: A total of 64 patients aged less than 18 years old with pro-BALL were enrolled. Clinical characteristics, therapeutic effect and prognostic factors were retrospectively analyzed. RESULTS: Pro-B-ALL occurred in 6.23% (64/1 028) of pediatric ALL. Among the 64 patients, 35 were male and 29 were female. The median age was 7.0 years (range 0.4-16.0 years) at diagnosis, of which 39% and 6% were ≥ 10 years old and < 1 year old respectively. The median WBC count was 25.5×10 CONCLUSIONS Pediatric pro-B ALL is a heterogeneous disease with clinical and biological diversity. Biological characteristics, such as immunological markers, genetic alterations, and MRD at 3 months after chemotherapy may be important factors for the long-term prognosis.
Adolescent ; Antigens, CD/genetics* ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Histone-Lysine N-Methyltransferase/genetics* ; Humans ; Infant ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Neoplasm, Residual/diagnosis* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the expression of Wilms'tumor 1 () gene in patients with acute myeloid leukemia (AML), and to explore its application in predicting prognosis of AML in patients with wild or mutated nucleophosmin 1() and Fms-like tyrosine kinase 3-internal tandem duplication (). METHODS: One hundred and sixty-seven newly diagnosed AML patients(exclued M3 type) were enrolled in this study. The survival of patients were analyzed with Kaplan-Meier method. The clinical data, laboratory findings and the survival of patients were analyzed and compared between patients with high expression (high- group) and those with low expression (low- group), as well as among the patients with or wild type and mutants. RESULTS: The overall response rates (ORR) in high- and low- groups were 65.9% (83/126) and 95.1% (39/41), respectively (<0.01). Compared with the low- group, the high- group had lower 2-y overall survival (OS) rate (46.1% vs. 75.2%, <0.05) and 2-y disease free survival (DFS) rate (43.5% vs. 68.5%, <0.05). After induction chemotherapy, the patients with decreased gene expression ≥ 1log was associated with higher ORR and 2-y OS rate (all <0.05), but the advantage of 2-y DFS rate was not shown (>0.05). In patients with wild type, the high- group had inferior ORR and 2-y OS rate (all <0.05), while in the patients with wild type, the high- group had inferior ORR, 2-y OS rate and 2-y DFS rate (all <0.05). In patients with or FLT3 -ITD mutations, the expression had no significantly predicting values in treatment efficacy and survival (all >0.05). CONCLUSIONS gene overexpression indicated poor prognosis of AML patients; the patients with decreased gene expression ≥ 1 log after the first induction therapy show better prognosis than those with<1 log. The gene expression level at diagnosis can be used as an unfavorable prognostic factor for AML patients with or wild types.
Disease-Free Survival ; Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; mortality ; Mutation ; Nuclear Proteins ; genetics ; Prognosis ; WT1 Proteins ; genetics ; fms-Like Tyrosine Kinase 3 ; genetics

Adult ; CCAAT-Enhancer-Binding Proteins/genetics* ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Neoplasm, Residual/diagnosis* ; Nuclear Proteins/genetics* ; Nucleophosmin ; Prognosis ; Remission Induction ; fms-Like Tyrosine Kinase 3/genetics*

No abstract available.
Bone Marrow/pathology ; Chromosomes, Human, Pair 12 ; Chromosomes, Human, Pair 9 ; Core Binding Factor Alpha 2 Subunit/*genetics ; DNA/metabolism ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/*genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion/*genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Translocation, Genetic

No abstract available.
Aged, 80 and over ; Base Sequence ; Bone Marrow/pathology ; DNA/chemistry/metabolism ; Female ; Fusion Proteins, bcr-abl/*genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/*genetics ; Multiplex Polymerase Chain Reaction ; Protein Isoforms/genetics ; Sequence Analysis, DNA

OBJECTIVETo explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC).

METHODSBone marrow aspirates of 2 patients with CML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations (CNV) were analyzed by single nucleotide polymorphism array (SNP array) in case 1. The results were confirmed with fluorescence in situ hybridization (FISH). Variations of acute lymphoblastic leukemia-related genes including CDKN2A/AB and PAX5 were detected by multiplex ligation-dependent probe amplication (MLPA).

RESULTSDeletions and duplications on derivative chromosome 9 detected by FISH were confirmed by SNP array analysis. The distances between the BCR/ABL fusion signals on the idic(Ph) chromosomes in the two patients have differed greatly. The idic(Ph) in the second patient was supposed to be formed by two Ph chromosomes joined at their q terminals, where as the idic(Ph) in the first patient have been shown to be fused at the satellite regions of their p arms.

CONCLUSIONThe idic(Ph) chromosomes presented in CML-BLC may predict resistance to Imatinib and response to Dasatinib.

Blast Crisis ; diagnosis ; genetics ; therapy ; Chromosome Aberrations ; Chromosome Banding ; Chromosome Deletion ; Chromosome Duplication ; Chromosomes, Human, Pair 9 ; genetics ; DNA Copy Number Variations ; Fatal Outcome ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; genetics ; therapy ; Male ; Middle Aged ; Philadelphia Chromosome

No abstract available.
Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Bone Marrow Cells/cytology/pathology ; Female ; Flow Cytometry ; Fusion Proteins, bcr-abl/*genetics ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Humans ; Immunophenotyping ; Leukemia/*diagnosis/etiology ; Lymphoma, Large B-Cell, Diffuse/*drug therapy ; Phenotype ; Rituximab/administration & dosage