1.New insight into DNA methylation in CML and its effect on clinical outcome--review.
Journal of Experimental Hematology 2008;16(6):1482-1486
All kinds of tumors have their specific DNA methylation patterns. The study of DNA methylation changes in chronic myelogenous leukemia includes (1) the hypomethylation of carcinogenic gene, (2) the hypermethylation of tumor-suppressing gene, and (3) the hypermethylation of fusion gene. In this paper, DNA methylation change in chronic myeloid leukemia (CML) and its role in clinical stages and evaluation of prognosis were reviewed so as to illuminate the relationship between DNA methylation and CML.
DNA Methylation
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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diagnosis
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genetics
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pathology
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Prognosis
3.Are leukemic patient bone marrow mesenchymal stem cells malignant?.
Zheng-Jun XIE ; Deng-Ming HU ; Wang-San-Bin ; Bo YIN ; Wei-Yang ZHENG ; Bing XU ; Xiao-Lan XU ; Rong LIN ; Ru FENG ; Shu-Yun ZHOU
Journal of Experimental Hematology 2007;15(5):913-918
The study was aimed to explore whether there are leukemic characteristics in the bone marrow mesenchymal stem cells (BMMSC) from leukemic patients as compared with normal controls. The mesenchymal stem cells from bone marrow of normal volunteers and patients with APL and CML were isolated, then cultured and proliferated in vitro. The morphology, growth curve and cell surface markers of two different sources mesenchymal stem cells were investigated for detecting whether the bone marrow mesenchymal stem cells derived from leukemia patients have the specific abnormal fusion gene of leukemia cells through fluorescent in situ hybridization. The results indicated that there was no significant difference between the mesenchymal stem cells derived from different subjects, the bone marrow mesenchymal stem cells derived from leukemia patients did not have the clonal malignant fusion gene as seen in the leukemia cells. Taken altogether, mesenchymal stem cells derived from leukemia patients had no biological differences as compared with those from normal volunteers, and no malignant clonal abnormality was found. It is concluded that mesenchymal stem cells derived from leukemia patients as an alternative vehicle may be used for assistant of autologous hematopoietic stem cell transplantation or cell therapy and gene therapy.
Bone Marrow Cells
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cytology
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Cells, Cultured
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Fusion Proteins, bcr-abl
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genetics
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Humans
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In Situ Hybridization, Fluorescence
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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genetics
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pathology
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Leukemia, Promyelocytic, Acute
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genetics
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pathology
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Mesenchymal Stromal Cells
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pathology
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Oncogene Proteins, Fusion
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genetics
5.Four Cases of Chronic Myelogenous Leukemia in Mixed Phenotype Blast Phase at Initial Presentation Mimicking Mixed Phenotype Acute Leukemia with t(9;22).
Woojin CHOI ; Myungshin KIM ; Jihyang LIM ; Kyungja HAN ; Seok LEE ; Jae Wook LEE ; Nack Gyun CHUNG ; Yonggoo KIM
Annals of Laboratory Medicine 2014;34(1):60-63
No abstract available.
Acute Disease
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Child
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Chromosomes, Human, Pair 22
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Chromosomes, Human, Pair 9
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Female
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Fusion Proteins, bcr-abl/genetics
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Humans
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In Situ Hybridization, Fluorescence
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Leukemia/*genetics/pathology
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics/pathology
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Male
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Middle Aged
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Phenotype
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*Translocation, Genetic
6.Expression of RHBDD1 gene in patients with chronic myeloid leukemia and its clinical significance.
Ya-Ni LIN ; Fu-Min GUI ; Hui SHEN ; Fang WANG ; Zeng CAO ; Qing-Hua LI ; Jian-Xiang WANG ; Tian-Xiang PANG
Journal of Experimental Hematology 2013;21(1):12-15
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
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metabolism
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pathology
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Case-Control Studies
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Female
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Gene Expression
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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genetics
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metabolism
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pathology
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Male
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Middle Aged
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Serine Endopeptidases
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genetics
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metabolism
7.Biological characteristics of Wt1 gene in relation to Ph(+) leukemia cell line K562.
Yan LI ; Xiao-Yan LI ; Lin WANG ; Zheng TIAN ; Qing RAO ; Hai-Rong JIA ; Hui-Jun WANG ; Min WANG ; Ying-Chang MI
Journal of Experimental Hematology 2010;18(3):564-569
Wt1 is a dual-function gene involved in hematopoiesis, leukemogenesis and prognosis for leukemia. This gene is highly expressed in acute myeloid leukemia (AML) and the progression of chronic myelogenous leukemia (CML). It was reported elsewhere that high level of wt1 expression indicated worse prognosis for leukemia. Wt1 gene functions are different due to its subcellular localization. This study was aimed to investigate the expression and localization of wt1 mRNA and WT1 protein, and explore the effects of wt1 inhibitor, curcumin, on K562 cell proliferation, cell cycle and its possible mechanisms. MTT method was used to detect cell proliferation; flow cytometry was used to analyze the alteration of cell cycle, and the immunofluorescence and Western blot technology were performed to observe the subcellular localization of WT1 protein. The transcripts of wt1 and bcr/abl p210 was analyzed by real-time PCR. The results showed that wt1 mRNA and its protein were both highly expressed in K562 cells. The curcumin and imatinib (Glevec) both inhibit the cell proliferation resulting in the G(2)/M and G(0)/G(1) phase arrest respectively. Meanwhile, the transcripts of wt1 and bcr/ablp210 genes decreased greatly after being treated with the two inhibitors above. It is concluded that the alteration of wt1 gene affects the biological characteristics of Ph(+) K562 cells, such as cell proliferation, cell cycle and so on. Gene wt1 is expected to be further studied as a new therapy target in Ph(+) leukemias.
Cell Cycle
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Cell Proliferation
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Curcumin
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pharmacology
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Humans
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K562 Cells
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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genetics
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metabolism
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pathology
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RNA, Messenger
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genetics
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WT1 Proteins
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genetics
8.Leukemia stem cells: the root of chronic myeloid leukemia.
Protein & Cell 2015;6(6):403-412
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
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Chemokines
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metabolism
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Epigenesis, Genetic
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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genetics
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metabolism
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pathology
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Neoplastic Stem Cells
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metabolism
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pathology
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Transcription Factors
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metabolism
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Tumor Microenvironment
9.Expression of XIAP gene in chronic myeloid leukemia and its clinical significance.
Journal of Experimental Hematology 2011;19(2):321-323
This study was purpose to investigate the expression of XIAP mRNA in chronic myeloid leukemia (CML) and to explore its significance in the advance and prognosis of CML. The chromosomal karyotype analysis and detection of XIAP mRNA were performed by the technique of chromosomal R banding and real time PCR in 71 patients with CML and 10 healthy controls. The results showed that there was a significant increase of XIAP mRNA expression in accelerated and blastic phase of the CML, compared with the patients in chronic phase (t = 9.10, 9.30, p < 0.01). Moreover, the difference of XIAP mRNA expression level was not statistically significant in different karyotype groups. It is concluded that the XIAP gene expression in accelerated and blastic phases of CML patients obviously increases, XIAP gene is closely related to the advance of CML.
Adult
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Case-Control Studies
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Female
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Gene Expression
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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genetics
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pathology
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Male
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Prognosis
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X-Linked Inhibitor of Apoptosis Protein
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genetics
10.Effect of heat stress on expression of gp96 in K562 cell line of the chronic myeloid leukemia and its significance.
Xin WANG ; Bin SHI ; Shen-Wu WANG ; Jian-Qiang DONG ; Jian-Ying CUI ; Shu-Xia HAN
Journal of Experimental Hematology 2006;14(4):667-672
This study was purposed to investigate the effect of different heat stress conditions on expression level of heat shock protein gp96 in K562 cell line of chronic myeloid leukemia in order to provide experiment basis for seeking optimal heat stress condition increasing extraction amount of gp96 from K562 cells. The expression changes of gp96 in K562 cell line was detected by immunocytochemistry under 38, 40, 42, 44, 46 and 48 degrees C for 30 minutes in water, by flow cytometry under 40, 44, 48 and 52 degrees C for 30 minutes in water, by Western blot under 40, 44, 48 and 52 degrees C for 30 minutes in water. Immunocytochemistry assay showed that gp96 existed mainly in cytoplasm. The peak of gp96 expression was at 30 minutes after 48 degrees C in water. The result of flow cytometry was consistent to immunocytochemistry detection results under temperatures 40, 44, 48 and 52 degrees C (P < 0.01). Western blot showed that detection result was the same as the immunocytochemistry and flow cytometry detections. In conclusion, the expression of gp96 in K562 cell line reached peak at 30 minutes after 48 degrees C in water. This condition may be an effective preparative condition for extraction of gp96 from K562 cells.
Antigens, Neoplasm
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biosynthesis
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genetics
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Blotting, Western
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Flow Cytometry
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Heat-Shock Response
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Humans
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Immunohistochemistry
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K562 Cells
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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metabolism
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pathology