HOXA9 and MEIS1 gene overexpression in the diagnosis of childhood acute leukemias: Significant correlation with relapse and overall survival
Maria AdamakiGeorge Ι. LambrouAnastasia AthanasiadouSpiros VlahopoulosAthanasios G. PapavassiliouMaria Moschovi
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Pathogenesis of atypical leukemia (hypoplastic leukemia and smoldering acute leukemia) is still unknown. The author intended to find the factors inducing its unique clinical course by comparing 5 cases of atypical leukemia with the same numder of typical acute leukemia with respect to their blasts cell size, laveling index with (3)H-thymidine and pattern of tissue growth by the bone marrow culture method devised by us. And obtained the following results. 1) The size of 100 blasts chosen randomely out of the bone marrow smear prepared from 5 cases of atypical leukemia was compared with those of typical acute leukemia. The mean val-ue of the former group was 41.9±12.3, while that of the latter was 61.4±16.7. There fore, the size of blasts in the atypical leukemia proved to be somewhat smaller than those of the typical acute leukemia. 2) The mean value of laveling index with (3)H-thymidine of the blasts in the bone marrow of the former group was 6.4% , while that of the latter was 12.9% . 3) The growth pattern of the bone marrow tissue from the 5 patients with atypical leukemia was as follows: The bone marrow explants from these patients were generally hypoplastic, consisting of an increase of fat cells intermingled with several foci scattered made of leukemic blasts. The growth zone revealed much lower cell density than that of the typical acute leukemia. The margin of the growth zone, however, sharply bordered and similar to the pattern of typical acute leukemia. Cells observed predominantly in the growth zone composed of immature leukemic cells and mature lymphocytes throughout the culture period of 24-48 hours. From these results, it is assumed that most of leukemic blasts in the bone marrow of the patients with atpical leukemia are dormant cells, i.e. belong to a nondividing compartment, and reduced multiplication rate is closely related to their mild clinical courses.
Thymidine
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Pathogenesis of atypical leukemia (hypoplastic leukemia and smoldering acute leukemia) is still unknown. The author intended to find the factors inducing its unique clinical course by comparing 5 cases of atypical leukemia with the same numder of typical acute leukemia with respect to their blasts cell size, laveling index with 3H-thymidine and pattern of tissue growth by the bone marrow culture method devised by us. And obtained the following results.1) The size of 100 blasts chosen randomely out of the bone marrow smear prepared from 5 cases of atypical leukemia was compared with those of typical acute leukemia. The mean value of the former group was 41.9±12.3, while that of the latter was 61.4±16.7. Therefore, the size of blasts in the atypical leukemia proved to be somewhat smaller than those of the typical acute leukemia.2) The mean value of laveling index with 3H-thymidine of the blasts in the bone marrow of the former group was 6.4%, while that of the latter was 12.9%.3) The growth pattern of the bone marrow tissue from the 5 patients with atypical leukemia was as follows: The bone marrow explants from these patients were generally hypoplastic, consisting of an increase of fat cells intermingled with several foci scattered made of leukemic blasts. The growth zone revealed much lower cell density than that of the typical acute leukemia. The margin of the growth zone, however, sharply bordered and similar to the pattern of typical acute leukemia. Cells observed predominantly in the growth zone composed of immature leukemic cells and mature lymphocytes throughout the culture period of 24-48 hours.From these results, it is assumed that most of leukemic blasts in the bone marrow of the patients with atpical leukemia are “dormant cells”, i.e. belong to a nondividing compartment, and reduced multiplication rate is closely related to their mild clinical courses.
Childhood leukemia
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The objective of this study was to investigate the expression and function of indoleamine 2, 3-dioxygenase (IDO) in leukemia. The IDO expressions in human acute monocyte leukemia (M(5)) and acute lymphocyte leukemia (ALL) were detected by immunofluorescence staining. Constructed leukemia mouse model was used to observe whether the IDO inhibitor, 1-methyl tryptophan (1-MT), has any effect in treating leukemia. The experimental group were fed with 1-MT solution every day while the mice in control group had no further treatment. The results showed that the average ratios of IDO expression were 29.4 +/- 11.2% in M(5) patients and 24.7 +/- 7.96% in ALL patients respectively. After statistical test, IDO expression level in leukemia cells was significantly higher than that of normal mononuclear cells. The tumor decreased gradually in mice treated with 1-MT. At the terminal point of the experiment (88 days after vaccination), the average survival time in the experimental group was 42.3 days while the mice in control group only lived 15.1 days in average, which difference was statistically significant (P < 0.05). Some of the leukemia mice in the experimental group long-term survived without tumor (more than three months after vaccination). It is concluded that human acute monocyte leukemia (M(5)) and acute lymphocyte leukemia (ALL) express IDO, and both can be treated by 1-MT in mice.
Indoleamine 2,3-dioxygenase
Acute monocytic leukemia
Monocyte
Acute myelomonocytic leukemia
Monocytic leukemia
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Pathogenesis
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Objective:To investigate the expression of MMP-2 and MMP-9 in acute leukemia and normal control and explore the relationship among MMP-2、MMP-9 and leukemia pathogenesis and infiltration.Method:The expression of MMP-2 and MMP-9 in bone marrow cells of untreated acute leukemia, relapse stage of acute leukemia, complete remission (CR) stage of acute leukemia and normal control were examined by in situ hybridization.Result:The positive rate of MMP-2 and MMP-9 in untreated, especially with infiltration and relapse stage of acute leukemia are significantly higher than that in CR stage of acute leukemia and normal control, the positive rate of MMP-2 and MMP-9 in untreated acute lymphoblastic leukemia(ALL) and acute nonlymphoblastic leukemia (ANLL) (M_4+M_5)group are significantly higher than that in ANLL (non M_4+M_5 )group.Conclusion:MMP-2 and MMP-9 may play an important role in leukemia pathogenesis and infiltration by enhancing the degradation of ECM.
Infiltration (HVAC)
Pathogenesis
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Chronic leukemia
White blood cell
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Hematology
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To investigate the expression levels of serum sICAM-1 and their clinical significances in patients with hyperleukocytic acute leukemia(HLAL).The serum levels of sICAM-1 in 30 hyperleukocytic acute leukemia and 20 non-hyperleukocytic acute leukemia were detected by ELISA,compared with 20 healthy persons as the control group.The expression of sICAM-1 in patients with hyperleukocytic acute leukemia and non-hyperleukocytic acute leukemia were significantly higher than those in control group,expecially in hyperleukocytic acute leukemia.Over expression of sICAM-1 may play a key role in the genesis and progression of hyperleukocytic acute leukemia.
Clinical Significance
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Objective To explore the role and the relationship between tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) receptor DR5 and Ki67 on acute leukemia cells.Methods Bone marrow mononuclear cells(BMMNC) from 20 cases of acute leukemia(acute leukemia group) and 10 cases of non-malignant hematological diseases(control group) were cultured for 72 hours,the expression of DR5 was analyzed by flow cytometry,and the expression of Ki67 by immunocytochemical staining.Results The expression of Ki67 on BMMNC from acute leukemia cells was significantly higher than that of control group 32.3±8.2 vs 15.4±3.9(P0.05).The expression of TRAIL-DR5 was low and there was no significant difference as compared with that of control group,12.2±4.3 vs 9.9±2.3(P0.05).The expression of Ki67 was negatively correlated with that of TRAIL-DR5(r=-0.459,P0.05).Conclusion The expression and the relationship of TRAIL receptor DR5 and Ki67 on acute leukemia cells suggest the abnormality in the apoptosis or proliferation of leukemia cells.The simultaneous assays of the expression of DR5 and Ki67 on acute leukemia cells have a better predictive value in the pathogenesis of acute leukemia than checking singularly.
Pathogenesis
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