The relationship between glutathione S-transferases (GSTs) M1, T1 genotype and childhood acute lymphoblastic leukemia (ALL) was investigated. GSTM1 and GSTT1 genotypes in genomic DNA from 67 children with ALL and 146 healthy controls were analyzed by using the multiplex polymerase chain reaction (PCR). The frequencies of GSTM1, M1-T1 null genotypes in ALL children were significantly higher than in the healthy controls (76.12% versus 52.74%, OR=2.856, P<0.001; 50.74% versus 24.66%, OR=3.148, P<0.001, respectively). However, there was no significant relationship between GSTT1 null genotype and ALL of children (61.19% versus 49.32%, OR=1.621, P>0.05). It was suggested that GSTM1 null genotype might be a risk genotype of childhood ALL, while there as no correlation between GSTT1 null genotype and childhood ALL.
Genotype ; Glutathione Transferase/*genetics ; Leukemia, Lymphocytic, Acute/*genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic/*genetics

The expression of the WT-1 gene which is found exclusively in human leukemic blasts frequently disappears from bone marrow of leukemia patients in complete remission (CR). Using semiquantitative RT-PCR, we investigated the expression of the WT-1 gene in peripheral bloods (PBs) of 33 patients with acute leukemia (AML 26; ALL 7) and monitored its expression after achievement of CR. None of the 6 normal controls expressed detectable levels of WT-1 transcripts (< 10(-4), background level), whereas 31 (93.9%) of 33 patients expressed variable levels of WT-1 transcripts (range, 10(-4) to 10(1)) at diagnosis. The level of WT-1 expression was not different between AML and ALL. By monitoring WT-1 gene expression in PB of 31 patients during CR, 5 patients relapsed (two from the 18 patients with undetectable levels of WT-1 gene expression and three from the 13 with WT-1 gene expression in low levels). Three of the 5 relapsed patients showed preceding reappearance or rise of WT-1 gene expression. From these results, we reconfirmed that the WT-1 gene is a pan-acute leukemic marker, which can be used to monitor minimal residual leukemia (MRL) after chemotherapy or in patients with CR.
Gene Expression/physiology* ; Human ; Leukemia, Lymphocytic, Acute/genetics* ; Leukemia, Lymphocytic, Acute/blood* ; Leukemia, Myelocytic, Acute/genetics* ; Leukemia, Myelocytic, Acute/blood* ; Neoplasm, Residual ; Nephroblastoma/genetics* ; Polymerase Chain Reaction ; Transcription, Genetic ; Tumor Markers, Biological

The bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis. This study investigated the presence of the BLV in leukemia (179 acute lymphoblastic leukemia, 292 acute myeloid leukemia and 46 chronic myelogenous leukemia cases) and 162 lung cancer patients (139 adenocarcinoma, 23 squamous cell carcinoma) to determine if the BLV is a causative organism of leukemia and lung cancer in Koreans. A BLV infection was confirmed in human cells by PCR using a BLV-8 primer combination. All 517 cases of human leukemia and 162 lung cancer were negative for a PCR of the BLV proviral DNA. In conclusion, although meat has been imported from BLV endemic areas, the BLV infection does not appear to be the cause of human leukemia or lung cancer in Koreans. These results can be used as a control for further studies on the BLV in Koreans.
Acute Disease ; Adenocarcinoma/virology ; Cell Line ; DNA, Viral/*genetics/isolation & purification ; Humans ; Korea ; Leukemia/*virology ; Leukemia Virus, Bovine/*genetics ; Leukemia, Lymphocytic, Acute/virology ; Leukemia, Myeloid/virology ; Leukemia, Myeloid, Chronic/virology ; Lung Neoplasms/*virology ; Polymerase Chain Reaction/methods ; Proviruses/*genetics

The aim of this study was to investigate the nucleotide sequence of one distinct fusion transcript of sil-tal1 in childhood T-ALL. The PCR product was cloned into plasmid vector and then sequenced. Genomic DNA was analyzed with PCR using the designed primer pairs representing distinct sequences. The product was sequenced and analyzed with database. The results indicated that 4 different fusion transcripts were detected at cDNA level, in which a part of exons or introns of sil are reserved respectively, and some additions and deletions existed. After analyzing genomic DNA sequence of leukemic cells, the breakpoint in gene sil of this case was proved to be different at DNA level from references. Hence, the sil-tal1 rearrangement was defined to be a new type. It is concluded tal1 rearrangement of leukemic cells in this case is a new type, which expresses classical and at least 3 variant fusion transcripts, presumably caused by extraordinary mechanisms of splicing and transcription in leukemic stem cells.
Base Sequence ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Child ; DNA Breaks ; DNA, Neoplasm ; genetics ; Humans ; Leukemia-Lymphoma, Adult T-Cell ; genetics ; Male ; Oncogene Proteins, Fusion ; genetics ; Proto-Oncogene Proteins ; genetics ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Transcription Factors

The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to beta-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1 %, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.
Vault Ribonucleoprotein Particles/*genetics ; Survival Rate ; RNA, Neoplasm/genetics ; RNA, Messenger/genetics ; Prognosis ; Neoplasm Proteins/*genetics ; Multidrug Resistance-Associated Proteins/*genetics ; Middle Aged ; Male ; Leukemia, Myelocytic, Acute/drug therapy/genetics/mortality ; Leukemia, Lymphocytic, Acute/drug therapy/genetics/mortality ; Leukemia/drug therapy/*genetics/mortality ; Infant ; Humans ; *Genes, MDR ; Gene Expression ; Female ; Child, Preschool ; Child ; Base Sequence ; Aged ; Adult ; Adolescent

Objective: To assess the clinical characteristics and prognosis of patients with SIL-TAL1-positive T-cell acute lymphoblastic leukemia (T-ALL) . Methods: The clinical data of 19 SIL-TAL1-positive T-ALL patients admitted to the First Affiliated Hospital of Soochow University between January 2014 and February 2022 were retrospectively computed and contrasted with SIL-TAL1-negative T-ALL patients. Results: The median age of the 19 SIL-TAL1-positive T-ALL patients was 15 (7 to 41 years) , including 16 males (84.2%) . SIL-TAL1-positive T-ALL patients had younger age, higher WBC, and hemoglobin compared with SIL-TAL1-negative T-ALL patients. There was no discrepancy in gender distribution, PLT, chromosome abnormality distribution, immunophenotyping, and complete remission (CR) rate. The 3-year overall survival (OS) was 60.9% and 74.4%, respectively (HR=2.070, P=0.071) . The 3-year relapse-free survival (RFS) was 49.2% and 70.6%, respectively (HR=2.275, P=0.040) . The 3-year RFS rate of SIL-TAL1-positive T-ALL patients was considerably lower than SIL-TAL1-negative T-ALL patients. Conclusion: SIL-TAL1-positive T-ALL patients were connected to younger age, higher WBC, higher HGB, and poor outcome.
Adolescent ; Adult ; Humans ; Male ; Young Adult ; Chromosome Aberrations ; Oncogene Proteins, Fusion/genetics* ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence ; Retrospective Studies ; T-Cell Acute Lymphocytic Leukemia Protein 1/genetics* ; T-Lymphocytes ; Female ; Child

OBJECTIVE: To analyze the polymorphisms of glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) gene exon 14, GPI-PLD activity of leucocyte in the peripheral blood,and the relationship in leukemia patients of Han nationality in Hunan. METHODS: Both 96 leukemia patients and 96 healthy persons of Han nationality in Hunan were researched [including 48 acute non-lymphocytic leukaemia (ANLL) patients as group A, 31 acute lymphoblastic leukaemia (ALL) patients as group B, 12 chronic granulocytic leukaemia (CML) patients as group C, 5 chronic lymphocytic leukaemia (CLL) patients as group D]. The polymorphisms were analyzed by PCR-SSCP and sequencing;. and GPI-PLD activities were determined by GPI-anchored placental alkaline phosphatase (PLAP) as substrate and triton-X114 partioning. RESULTS: There were four variations in the coverage of GPI-PLD gene exon 14 of leukemia patients and healthy persons. The codons of variation were: 1257 C-->T, 1298 T-->C, 1218 C-->A, 1257 C-->A. The total various frequency in leukemia patient and healthy person, which was determined by SSCP, was 28.12% and 20.83%. On the basis of the percentage of GPI-anchored PLAP conversion, the leucocyte GPI-PLD activities of the 96 leukemia patients were measured. Compared with the 96 healthy controls, the leukocyte GPI-PLD activites of ANLL and CLL patients were significantly increased; the acticities of ALL and CML patients were significantly reduced. CONCLUSION Leukocyte GPI-PLD gene in the peripheral blood, which belongs to healthy persons and leukemia patients of Han nationality in Hunan, is polymorphism. The leukocyte GPI-PLD activities in the four groups are remarkable.
Adolescent ; Adult ; Aged ; Base Sequence ; Exons ; genetics ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Molecular Sequence Data ; Phospholipase D ; genetics ; metabolism ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Single-Stranded Conformational ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics

This study was aimed to investigate the expression level of CIAPIN1 mRNA in leukemia patients and explore its significance in leukemias. The fresh bone marrow was collected from 112 newly diagnosed leukemia patients, the total RNA was extracted by means of TRIzoL, the cDNA was synthesized, the expression of CIAPIN1 mRNA was detected by real-time quantitative PCR using β-actin as internal reference; 10 normal healthy persons were selected as controls. The results showed that the expression of CIAPIN1 mRNA was statistically higher in acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and chronic phase chronic myeloid leukemia (CML) patients than that in normal persons (p < 0.05); but there was no statistical difference between chronic lymphocytic leukemia (CLL) and normal persons (p > 0.05). It is concluded that the CIAPIN1 gene higher expresses in MNC of newly diagnosed leukemia patients, up-regulation of CIAPIN1 expression may play an important role in pathogenesis of leukemia.
Adult ; Bone Marrow Cells ; metabolism ; Case-Control Studies ; Female ; Gene Expression Regulation, Leukemic ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Leukemia ; genetics ; metabolism ; pathology ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Young Adult

To evaluate the expression of cyclin dependent kinase inhibitor P27(Kip1) in leukemia and to investigate its clinical significance, the P27(Kip1) protein in bone marrow or peripheral blood samples from 82 cases of leukemia was measured by Western blot and enhanced chemoluminescence (ECL). The results showed that the expression of P27(Kip1) protein in ALL was higher than that in ANLL (P = 0.033) and also that in CML (P = 0.008). P27(Kip1) expression in CLL was higher than that in CML too (P = 0.017). In acute leukemia, the effective rate (CR and PR) of initial chemical therapy in the group of P27(Kip1) > 0.655 was higher than that in the group of P27(Kip1) < or = 0.655, P = 0.041. For ANLL and ALL patients, the survival time in the group of P27(Kip1) > 0.655 was longer than that in the group of P27(Kip1) < or = 0.655, P = 0.0065. There were similar statistical significance for ANLL and ALL patients, P = 0.0271 and P = 0.0266 respectively. There was a negative correlation between chromosomal abnormalities and P27(Kip1) expression in ALL patients (r = -0.775, P = 0.04). The expression of P27(Kip1) protein appeared nothing to do with sex, age, white blood cell number, blast cell number in peripheral blood, serum LDH or uric acid. In conclusion, the expression level of P27(Kip1) protein is in relation to the effect of initial chemical therapy and survival time, so that the lower P27(Kip1) expression may associated with poor prognosis in acute leukemia.
Adolescent ; Adult ; Aged ; Blotting, Western ; Cell Cycle Proteins ; analysis ; Child ; Child, Preschool ; Chromosome Aberrations ; Cyclin-Dependent Kinase Inhibitor p27 ; Female ; Humans ; Leukemia ; drug therapy ; genetics ; metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; genetics ; metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; metabolism ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; metabolism ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; metabolism ; Survival Rate ; Tumor Suppressor Proteins ; analysis

The aims of this study were to estimate the incidences of BCR/ABL, MLL, TEL/AML1 rearrangements, and p16 deletions in childhood acute lymphoblastic leukemia (ALL), to identify new abnormalities, and to demonstrate the usefulness of interphase fluorescence in situ hybridization (FISH). We performed G-banding analysis and FISH using probes for BCR/ABL, MLL, TEL/AML1 rearrangements, and p16 deletions on 65 childhood ALL patients diagnosed and uniformly treated at a single hospital. Gene rearrangements were identified in 73.8% of the patients using the combination of G-banding and FISH, while the chromosomal abnormalities were identified in 49.2% using G-banding alone. Gene rearrangements were disclosed by FISH in 24 (72.7%) of 33 patients with normal karyotype or no mitotic cell in G-banding. Among the gene rearrangements detected by FISH, the most common gene rearrangement was p16 deletion (20.3%) and the incidences of others were 14.1% for TEL/AML1, 11.3% for MLL, and 1.8% for BCR/ABL translocations. Infrequent or new aberrations such as AML1 amplification, MLL deletion, ABL deletion, and TEL/AML1 fusion with AML1 deletion were also observed. We established the rough incidences of gene rearrangements in childhood ALL, found new abnormalities and demonstrated the diagnostic capability of interphase FISH to identify cryptic chromosome aberrations.
Adolescent ; Child ; Child, Preschool ; *Chromosome Aberrations ; Chromosome Banding ; DNA-Binding Proteins/*genetics ; Female ; Fusion Proteins, bcr-abl/*genetics ; Gene Deletion ; *Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Interphase ; Leukemia, Lymphocytic, Acute/*genetics ; Male ; Oncogene Proteins, Fusion/*genetics ; Protein p16/*genetics ; Proto-Oncogenes/*genetics ; Transcription Factors/*genetics ; Treatment Outcome