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

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

Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid, Chronic-Phase ; genetics ; Lymphoma ; classification ; diagnosis ; pathology ; Male ; Neoplasms ; genetics ; metabolism ; pathology ; Oncogene Proteins ; metabolism ; Prognosis ; Prostatic Neoplasms ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Translocation, Genetic ; Tumor Suppressor Proteins ; metabolism

The aim of this study was to investigate the expression status of the helicase antigen (HAGE) transcript and its clinical significance in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). The expression of HAGE cDNA in bone marrow mononuclear cells from AML and CML patients was detected by using real-time quantitative PCR. The results indicated that overexpression of HAGE transcript (117.12% - 9842.70%, median 434.96%) was detected in 14.8% (11/74) AML patients. AML patients with HAGE cDNA expression were significantly older than those HAGE-negative patients (median 67 and 45 years, respectively, p = 0.001). HAGE cDNA expression was more frequently present among the patients with acute monoblastic leukemia (M(4) and M(5), 7 of 20, 35.0%), compared to the patients with acute non-monoblastic leukemia (M(1), M(2), M(3) and M(6), 4 of 54, 7.4%) (p = 0.007). 28.6% (8/28) cases with normal karyotypes showed HAGE cDNA overexpression, significantly higher than 7.5% (3 of 40) in those with chromosomal abnormalities (p = 0.041). Overexpression of HAGE transcript was found in 9 (34.6%) CML cases and more frequently observed at accelerated phase and blast crisis (4/4, 100%) than that at chronic phase (5/22, 22.7%) (p = 0.008). It is concluded that HAGE cDNA expression is relevant to specific subtypes of AML and to the progression of CML.
Blast Crisis ; Bone Marrow Cells ; metabolism ; DEAD-box RNA Helicases ; genetics ; metabolism ; DNA, Complementary ; Gene Expression ; Humans ; Karyotype ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; metabolism ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Neoplasm Proteins ; genetics ; metabolism ; RNA, Messenger ; genetics

The study was purposed to investigate the expression of CD73 on bone marrow nucleated cells (BMMNC) in various leukemia subtypes and its relationship with cell differentiation of leukemia. Immunocytochemistry staining and Wright-Giemsa staining of BMMNC from 75 cases of leukemia, 11 cases of myelodysplastic syndrome (MDS), 13 cases of non-leukemic patients and 9 healthy adults were performed, and the CD73(+) ratio in BMMNC and its relationship with differentiation of leukemia cells were analyzed. The results showed that the ratios of CD73(+) in BMMNC of com-B ALL, pre-B ALL and PLL were significantly higher than those in B-CLL (p < 0.05). CD73(+) ratios in AML subtypes of M(1), M(2a), t (8; 21), t (15; 17), M(4) and M(5) were markedly higher than those in MDS respectively, but in M(6) and MDS were lower and had no statistical difference between them. CD73(+) ratios in T-ALL, B-CLL, M(6), MDS, non-leukemia patients and healthy adults were close to each other and all of them were lower than those in B-ALL and other AML subtypes. It is concluded that the expression of CD73 is associated with leukemia subtype, differentiation and development. The higher differentiation of leukemia cells, the lower of CD73 expression in myeloid and B lymphoid leukemia, but T-ALL does not meet this pattern.
5'-Nucleotidase ; metabolism ; Adolescent ; Adult ; Cell Differentiation ; Humans ; Leukemia ; metabolism ; pathology ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; Leukemia, Myeloid, Acute ; metabolism ; Myelodysplastic Syndromes ; metabolism ; Young Adult

Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Benzamides ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Drug Delivery Systems ; methods ; Gastrointestinal Stromal Tumors ; drug therapy ; Humans ; Imatinib Mesylate ; Indoles ; therapeutic use ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; Leukemia, Myeloid ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Mutation ; Neoplasms ; drug therapy ; genetics ; metabolism ; Piperazines ; therapeutic use ; Prednisone ; therapeutic use ; Pyrimidines ; therapeutic use ; Pyrroles ; therapeutic use ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Remission Induction ; Rituximab ; Vincristine ; therapeutic use

OBJECTIVETo identify and compare the expression profiles of differential proteins between chronic phase and blast crisis in chronic myeloid leukemia (CML) by proteomic analysis, and screen the proteins related to blast crisis.

METHODSThe total cellular proteins from the bone marrow cells at chronic phase (CP) and blast crisis (BC) in CML were separated by two-dimensional polyacrylamide gel electrophoresis (2-DE) and analyzed with ImageMaster 5.0 software to screen the differential protein spots. Differential protein spots were identified by mass spectrometry for peptide mass fingerprint in combination with database searching from SWISS-PROT. Then 3 protein spots were selected to verify at protein and mRNA levels by Western blot and semi-quantitative RT-PCR, separately.

RESULTSComparing gel pages from CML-CP and CML-BC, the expression of 13 protein spots decreased and 25 protein spots increased significantly in CML-BC. Twenty differential protein spots were identified by mass spectrometry and 15 were successfully determined. The results of Western blotting were similar to those of 2-DE and showed a high expression of hnRNPK, annexin A1 and RhoA. Semi-quantitative RT-PCR analysis showed that there was no correlation between the protein expression changes and mRNA levels of hnRNPK, annexin A1 and RhoA.

CONCLUSIONA group of proteins associated with blast crisis are obtained and the results may provide clues for further research to elucidate the role of these proteins in CML-BC carcinogenesis and to develop potential associated biomarkers.

Adult ; Aged ; Annexin A1 ; genetics ; metabolism ; Blast Crisis ; genetics ; metabolism ; Female ; Gene Expression Profiling ; Heterogeneous-Nuclear Ribonucleoprotein K ; Humans ; Leukemia, Myeloid, Chronic-Phase ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Proteomics ; methods ; RNA, Messenger ; metabolism ; Ribonucleoproteins ; genetics ; metabolism ; Young Adult ; rhoA GTP-Binding Protein ; genetics ; metabolism

To gain insight into the differential mechanism of gene promoter hypermethylation in acute and chronic leukemia, we identified the methylation status on one part of 5'CpG rich region of 8 genes, DAB2IP, DLC-1, H-cadherin, ID4, Integrin alpha4, RUNX3, SFRP1, and SHP1 in bone marrows from acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) patients. Also, we compared the methylation status of genes in AML and CML using methylation-specific PCR (MSP). The frequencies of DNA methylation of ID4, SFRP1, and SHP1 were higher in AML patients compared to those in CML patients. In contrast, no statistical difference between AML and CML was detected for other genes such as DLC-1, DAB2IP, H-cadherin, Integrin alpha4, and RUNX3. Taken together, these results suggest that these methylation-controlled genes may have different roles in AML and CML, and thus, may act as a biological marker of AML.
Adolescent ; Adult ; Aged ; CpG Islands ; *DNA Methylation ; Female ; Humans ; Inhibitor of Differentiation Proteins/*genetics/metabolism ; Intercellular Signaling Peptides and Proteins/*genetics/metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics/metabolism ; Leukemia, Myeloid, Acute/*genetics/metabolism ; Male ; Membrane Proteins/*genetics/metabolism ; Middle Aged ; Promoter Regions, Genetic ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/*genetics/metabolism

To gain insight into the differential mechanism of gene promoter hypermethylation in acute and chronic leukemia, we identified the methylation status on one part of 5'CpG rich region of 8 genes, DAB2IP, DLC-1, H-cadherin, ID4, Integrin alpha4, RUNX3, SFRP1, and SHP1 in bone marrows from acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) patients. Also, we compared the methylation status of genes in AML and CML using methylation-specific PCR (MSP). The frequencies of DNA methylation of ID4, SFRP1, and SHP1 were higher in AML patients compared to those in CML patients. In contrast, no statistical difference between AML and CML was detected for other genes such as DLC-1, DAB2IP, H-cadherin, Integrin alpha4, and RUNX3. Taken together, these results suggest that these methylation-controlled genes may have different roles in AML and CML, and thus, may act as a biological marker of AML.
Adolescent ; Adult ; Aged ; CpG Islands ; *DNA Methylation ; Female ; Humans ; Inhibitor of Differentiation Proteins/*genetics/metabolism ; Intercellular Signaling Peptides and Proteins/*genetics/metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics/metabolism ; Leukemia, Myeloid, Acute/*genetics/metabolism ; Male ; Membrane Proteins/*genetics/metabolism ; Middle Aged ; Promoter Regions, Genetic ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/*genetics/metabolism

In order to investigate the suppressor of cytokine signaling-1 (SOCS-1) expression in peripheral blood mononuclear cells (PBMNC) of patients with acute and chronic myeloid leukemia and analyze its clinical significance, RT-PCR method was used for detecting SOCS-1 mRNA expression in PBMNC of 50 newly diagnosed patients. The result showed that positive expressions of SOCS-1 were observed in 4 of 25 patients with AML (16.00%), in 11 of 25 patients with CML (44.00%) and none in 10 normal controls. The differences between patients with AML and normal controls, and between patients with CML and normal controls were statistically significant. In CML group, 2 out of 12 cases with non-progression (chronic phase), 9 of 13 cases with progression showed the positive expression, the difference between two subgroups was statistically significant. Those CML patients with SOCS-1 mRNA expression had poor response to IFN-alpha. When they transformed into accelerated phase, SOCS-1 mRNA expression was more persistently and frequently observed, and no response to IFN-alpha was observed. Most of them had very poor prognosis. It is concluded that the SOCS-1 mRNA can be detected in the PBMNC of the patients with acute and chronic myeloid leukemia. The SOCS-1 mRNA expression in the patients with CML is higher than that in patients with AML, and it is higher in accelerated phase and blast crisis significantly. This phenomenon is highly related to the reaction of IFN-alpha and prognosis.
Humans ; Interferon-alpha ; metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; metabolism ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; RNA, Messenger ; biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Suppressor of Cytokine Signaling 1 Protein ; Suppressor of Cytokine Signaling Proteins ; biosynthesis ; genetics