The study was aimed to explore the expression of stromal cell derived factor-1alpha (SDF-1alpha) and its receptor CXCR4, and their relationship with the extramedullary infiltration in acute lymphoblastic, grannulocytic and monocytic leukemia. 66 cases of acute leukemia included 31 cases of acute lymphoblatic leukemia (ALL), 20 cases of acute grannulocytic leukemia (M(2)) and 15 cases of acute monocytic leukemia (M(4)+M(5)). There were 41 cases with extramedullary infiltration and 25 cases without-extramedullary infiltration. Enzyme-linked immunoabsorbent assay (ELISA) and flow cytometry were used to determine expression of SDF-1alpha and CXCR4 respectively on leukemia cells in peripheral blood and bone marrow of different groups. The results showed that average plasma level of SDF-1alpha in the ALL, M(4)+M(5), M(2) patients and the normal control were 1317.87 +/- 220.76, 1339.79 +/- 187.06, 1063.70 +/- 190.74, 1908.34 +/- 135.55 (pg/ml) respectively. The average levels in the ALL, M(4)+M(5) and M(2) patients groups were lower than those in normal control group. Both levels in ALL and M(4)+M(5) patient groups were higher than that in M(2) patient group. The average levels of SDF-1alpha in patient group with extramedullary infiltration and patient groups without-extramedullary infiltration were 1252.49 +/- 263.12, 1234.91 +/- 185.50 (pg/ml) respectively. The former seemed as if higher than the latter, but without statistical significance. The MFI of CXCR4 expression in ALL, M(4)+M(5), M(2) patient group were 78.47 +/- 33.96, 67.21 +/- 24.29, 41.66 +/- 17.18, respectively. CXCR4 expression in ALL and M(4)+M(5) patient groups were higher than that in M(2) patient group (P > 0.05). There was no significant difference between the ALL and M(4)+M(5) patient group (P > 0.05). The MFI of CXCR4 expression in patients with extramedullary infiltration and patients without extramedullary infiltration were 81.72 +/- 27.63, 36.94 +/- 11.86 respectively. The former was higher than the latter (P < 0.05). It is concluded that the higher expression of CXCR4 on acute lymphoblatic and monocytic leukemia cells may be one of the molecular mechanisms of extramedullary infiltration in both kinds of leukemia. The average plasma levels of SDF-1alpha decreased in leukemia patients and this decrease not related to the extramedullar infiltration, which may be due to the SDF-1alpha local expression in the organ infiltrated.
Acute Disease ; Adolescent ; Adult ; Chemokine CXCL12 ; Chemokines, CXC ; biosynthesis ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Leukemia ; metabolism ; pathology ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Leukemic Infiltration ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; Receptors, CXCR4 ; biosynthesis ; genetics ; Stromal Cells ; metabolism

The purpose of this study was to investigate the expression feature of a human tumor related gene chp2 in leukemia primary cells and leukemia cell lines, real-time quantitative PCR (RQ-PCR) was performed to detect the expression level of chp2 gene in peripheral blood mononuclear cells from 10 healthy individuals (as control) and 24 cases of leukemia, and in 4 kinds of leukemia cell lines. The results showed that the detection rate of chp2 gene in 10 normal controls was 80%, positive expression was (0.744 +/- 0.682) x 10(5) cps/microl. The expression levels of chp2 mRNA leukemia primary cells and leukemia cell lines were significantly higher than that in the normal control (p < 0.05). The expression levels of chp2 mRNA were higher in AML cells (7 cases), CML cells (6 cases), ALL cells (7 cases) and CLL cells (4 cases), and their expression levels were (11.637 +/- 5.588), (6.122 +/- 3.785), (4.262 +/- 2.561) and (3.434 +/- 1.974) x 10(5) cps/microl respectively. Gene chp2 positively expressed in four kinds of leukemia cell lines, and the expression levels in K562 cells, Jurkat cells, HL-60 cells and M07e cells were (5.243 +/- 1.852), (4.463 +/- 1.621), (4.137 +/- 1.837) and (2.578 +/- 1.137) x 10(6) cps/microl respectively. The expression level in leukemia cell lines was higher than that in primary cells. It is concluded that the human tumor related gene chp2 expression in leukemia primary cells and leukemia cell lines significantly increase, which may play an important role in growth process of leukemia cells.
Calcium-Binding Proteins ; genetics ; metabolism ; HL-60 Cells ; Humans ; Jurkat Cells ; K562 Cells ; Leukemia ; genetics ; metabolism ; pathology ; Neoplasm Proteins ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism

This study was aimed to compare the expression level of eIF4E in patients with leukemia and normal controls, and to explore its role in leukemogenesis. White blood cells were collected in 76 leukemia patients and 10 healthy volunteers. The mRNA and protein expressions of eIF4E were detected by QT-PCR and Western blot in 39 cases of acute myeloid leukemia (AML), 15 cases of chronic myeloid leukemia (CML), 22 cases of acute lymphocytic leukemia (ALL) and 10 healthy volunteers as normal controls. The results demonstrated that compared with normal controls, the absolute expression levels of eIF4E mRNA increased in patients with AML, ALL and CML in blastic phase (P < 0.05), but had no significant change between groups of CML in chronic and accelerated phase although some increasing in group of CML in accelerated phase. The relative expression level of eIF4E mRNA had no significant change in AML, ALL, CML groups except the two subtypes of leukemia M4 and M5. Furthermore, the protein expression level in group of CML in accelerated phase and blastic phase and all acute leukemia patients including AML and ALL were higher than that in normal controls (P < 0.05). It is concluded that although its mRNA relative expressions had no significant change in most leukemia patients, the absolute expression level of eIF4E mRNA and its protein expression is up-regulated in most leukemia patients, which may play an important role in leukemogenesis, so the eIF4E may be a promising target for leukemia therapy and eIF4E-targeted therapy may be an option especially for the relapse and refractory leukemia.
Adolescent ; Adult ; Aged ; Case-Control Studies ; Eukaryotic Initiation Factor-4E ; genetics ; metabolism ; Female ; Humans ; Leukemia ; genetics ; metabolism ; pathology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; RNA, Messenger ; genetics ; Young Adult

To explore the expression spectra of apoptosis-related gene pnas-2 in normal tissues and acute leukemia (AL) patient tissues, the expressions of pnas-2 gene in tissues including heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, lymph node, thymus, leukocyte, bone marrow and fetal liver were detected by Northern blot. The expressions of pnas-2 in samples including 44 de novo, 9 non-CR, 27 CR and 12 relapsed AL patients were measured by real-time RT-PCR and Northern blot, and the expression levels of pnas-2 in normal and tumor tissues from 31 patients with malignancies were also detected. The results showed that pnas-2 was not expressed in the most tissues except in placenta. The results of real-time PCR indicated that pnas-2 expressions in samples of de novo, non-CR and relapsed patients ware significantly higher than that in CR, tumor tissues and normal tissues. In serial monitoring of 7 AL patients, the expression level of pnas-2 was high at first visit examination, but remarkably decreased after remission, and the pnas-2 expression level increased again when relapsed. It is concluded that the pnas-2 is specifically up-regulated in acute leukemia patients, which might be an oncogene and participate in leukemogenesis.
Acute Disease ; Apoptosis ; genetics ; Apoptosis Regulatory Proteins ; genetics ; metabolism ; Biomarkers, Tumor ; genetics ; Gene Expression Regulation, Leukemic ; Humans ; Leukemia ; pathology

This study was aimed to investigate the expression of RHBDD1 gene in patients with chronic myeloid leukemia (CML) and explore its clinical significance. The relative expression levels of RHBDD1 in bone marrow mononuclear cells of healthy controls and CML patients were detected by using real time PCR. The results showed that the expression level of RHBDD1 in CML patients was significantly higher than that in healthy controls. The expression level of RHBDD1 in CML patients with negative BCR/ABL p210 was remarkably higher than that in patients with positive BCR/ABL p210. In patients ≥ 50 years old RHBDD1 expression was lower than the patients < 50 years old. There were no significant relation of RHBDD1 expression with sex of patients. It is concluded that RHBDD1 gene may be involved in the pathogenesis and progression of CML, particularly reflects in the pathogenesis of the patients with negative BCR/ABL p210.
Bone Marrow Cells ; metabolism ; pathology ; Case-Control Studies ; Female ; Gene Expression ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Serine Endopeptidases ; genetics ; metabolism

The Pax5 gene encodes the B-cell-specific activator protein which is a key regulator in development and differentiation of B-cell. We studied the expression of Pax5 in hematologic malignancies to evaluate the diagnostic utility as a B cell marker. Materials included 70 B cell lymphomas, 26 T cell lymphomas, 53 acute leukemias, and 6 multiple myelomas (MMs). Representative areas from the paraffinembedded tissues were selected for tissue microarray, and the expressions of Pax5 was immunohistochemically evaluated. Pax5 was strongly expressed in most of the B cell lymphomas; 44 of 47 diffuse large B cell lymphomas (93.6%), 15 of 16 marginal zone B cell lymphomas (93.8%), all 3 mantle cell lymphomas, 2 follicular lymphomas, and 2 Burkitt's lymphomas (100%). However, Pax5 was expressed in only one of 26 T cell lymphomas. Among leukemias, it was expressed in 10 of the 14 B acute lymphocytic leukemias (ALLs) (72.4%), but also in 3 of the 6 T ALLs (50%), 13 of the 26 acute myelogenous leukemias (AMLs) (50%) and in all 3 ALL arising in chronic myelogenous leukemias and 4 mixed B ALL and AML. In MMs, Pax5 was negative in all cases. We concluded that Pax5 is very useful B cell marker in classification of lymphomas, but not of acute leukemias.
B-Lymphocytes/pathology/physiology ; DNA-Binding Proteins/genetics/*metabolism ; Human ; Leukemia/classification/*metabolism/pathology ; Lymphoma, Non-Hodgkin/classification/*metabolism/pathology ; Support, Non-U.S. Gov't ; Tonsil/cytology/metabolism/pathology ; Transcription Factors/genetics/*metabolism ; Tumor Markers, Biological/*metabolism

The DNA segment of the human acyl coenzyme A: cholesterol acyltransferasel (ACAT1) gene P7 promoter was amplified by PCR from human monocytic leukemia cell line (THP-1) and cloned to TA vector, then the positive clone was confirmed by restriction enzymes and sequencing. The targeted segment was subcloned to Firefly luciferase report vector pGL3-Enhancer. The recombinant plasmid pGL3E-P7 was transfected transiently into THP-1, then the expression of luciferase could be detected in THP-1 by pGL3E-P7 transfection. We successfully constructed luciferase reporter vector containing P7 promoter of the human ACAT1 gene, and established a new means to study the transcriptional regulation mechanisms of ACAT1 during atherosclerosis.
Cell Line, Tumor ; Chromosomes, Human, Pair 7 ; genetics ; Gene Expression Regulation ; Genes, Reporter ; genetics ; Genetic Vectors ; genetics ; Humans ; Leukemia, Monocytic, Acute ; pathology ; Luciferases, Firefly ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; Sterol O-Acyltransferase ; genetics ; metabolism ; Transfection

In order to study the relationship between the expression of glutathione S-transferase (GST) in leukemic cells and the chemoresistance in patients with acute leukemia, the expressions of GST activity and GST mRNA were measured according to spectrophotometric assay based on the use of 1-choloro-2, 4-dinitro benzene and in situ hybridization. The results were studied in correlation with some clinical and pathological data. Results showed that: 1. There is no significant differences between activities of the enzyme with the different leukemia types according to the FAB classification. 2. GST activity and GST mRNA expression in the patients, both untreated and relapse, were (4.5 +/- 1.0) U, 33.3% and (7.9 +/- 15) U, 66.3% respectively. 3. In 56 patients, GST activity was 1.7 +/- 0.7, 5.9 +/- 2.0 and 9.3 +/- 1.7 U and GST mRNA expression was 13.3%, 29.7% and 76.6%, respectively, in CR, PR and NR groups. The lowest values of GST activity and GST mRNA expression were observed in those patients who achieved complete remission. The highest values of GST activity and GST mRNA expression were observed in those patients with no response to treatment. It was concluded that the expression of GST in patients with acute leukemia is closely related to the chemosensitivities clinically. Determinations of GST activity and GST mRNA are useful for predicting the chemosensitivities and the prognosis of the disease.
Adolescent ; Adult ; Aged ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Glutathione Transferase ; genetics ; metabolism ; Humans ; Isoenzymes ; genetics ; metabolism ; K562 Cells ; Leukemia ; drug therapy ; enzymology ; genetics ; Leukemia, Lymphoid ; drug therapy ; enzymology ; genetics ; Leukemia, Monocytic, Acute ; drug therapy ; enzymology ; genetics ; Leukemia, Myeloid, Acute ; drug therapy ; enzymology ; genetics ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; enzymology ; genetics ; pathology ; RNA, Messenger ; genetics ; metabolism

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by a chromosome translocation that generates the Bcr-Abl oncogene encoding a constitutive kinase activity. Despite remarkable success in controlling CML at chronic phase by Bcr-Abl tyrosine kinase inhibitors (TKIs), a significant proportion of CML patients treated with TKIs develop drug resistance due to the inability of TKIs to kill leukemia stem cells (LSCs) that are responsible for initiation, drug resistance, and relapse of CML. Therefore, there is an urgent need for more potent and safer therapies against leukemia stem cells for curing CML. A number of LSC-associated targets and corresponding signaling pathways, including CaMKII-γ, a critical molecular switch for co-activating multiple LSC-associated signaling pathways, have been identified over the past decades and various small inhibitors targeting LSC are also under development. Increasing evidence shows that leukemia stem cells are the root of CML and targeting LSC may offer a curable treatment option for CML patients. This review summarizes the molecular biology of LSC and its-associated targets, and the potential clinical application in chronic myeloid leukemia.
Animals ; Chemokines ; metabolism ; Epigenesis, Genetic ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; metabolism ; pathology ; Neoplastic Stem Cells ; metabolism ; pathology ; Transcription Factors ; metabolism ; Tumor Microenvironment

CD4 Antigens ; metabolism ; CD56 Antigen ; metabolism ; Dendritic Cells ; pathology ; Diagnosis, Differential ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Hematologic Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Humans ; Immunohistochemistry ; Leukemia, Myeloid ; pathology ; Lymphoma, Extranodal NK-T-Cell ; pathology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; Skin Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; surgery