Adult Acute Leukemia Cells Research Articles

Significance of OCT3/4 and SOX2 antigens expression by leukemic blast cells in adult acute leukemia

ObjectiveThis study aimed to address the prognostic impact of SOX2 and OCT3/4 expression on adult acute leukemia patients’ outcomes.MethodsSOX2 and OCT3/4 expression by blast cells were evaluated by flow cytometry in 80 acute leukemia patients and 8 healthy controls.ResultsBaseline SOX2 and OCT3/4 expression were significantly higher in both ALL (P = < 0.001, P = 0.005 respectively) and AML patients (P < 0.001, P = 0.003 respectively) as compared to control, and decline at complete remission (CR) and elevated again at relapse. High SOX2 and OCT3/4 levels were significantly correlated with the presence of adverse risk stratification parameters.ConclusionOur findings indicated that both SOX2 and OCT3/4 could serve as biomarkers that could improve risk stratification of acute leukemia patients. Also, both SOX2 and OCT3/4 might be a therapeutic target, especially in resistant acute leukemia.

Expression and Clinical Significance of CC-chemokine Receptor 7 in Adult Acute Leukemia

To explore the expression of CC-chemokine Receptor 7 (CCR7) in adult acute leukemia patients, and to analyze the relationship of CCR7 expression with the clinical characteristics of patients. The expression of CCR7 in bone marrow samples from adult acute leukemia patients were detected by flow cytometry (FCM), the relationship of CCR7 expression with the clinical characteristics of patients such as sex, age, WBC count, blast cell ratio, CD56 expression, molecular biology, cell genetics, risk stratification, extramedullary infiltration was analyzed. The expression rate of CCR7 in adult ALL and AML patients was 36.8% and 9.6%, respectively, and the expression level of CCR7 in ALL patients was higher than that in AML patients (P < 0.05). The extramedullary infiltration rate was 100% and 41.7 % for CCR7 positive and negative groups of ALL, respectively (P < 0.05). While the mean fluorescence intensity (MFI) in extramedullary infiltration group of ALL was higher than that in none-extramedullary infiltration group of ALL (50.00 ± 10.42 vs 18.14 ± 1.39), respectively (P < 0.05). CCR7 is higher expressed in adult acute leukemia cells, moreover its expression rate in ALL is higher than that in AML, and the expression of CCR7 is related with extramedullary infiltration in ALL.

Effects of itraconazole plus doxorubicin on proliferation and apoptosis in acute myeloid leukemia cells

To explore the effects of itraconazole (ITC) plus adriamycin (ADM) on proliferation and apoptosis of acute myeloid leukemia cells in vitro. The growth inhibition effects of different concentrations of ITC, ADM or ITC (2, 6, 15 µmol/L) plus ADM (0.30, 0.75 µmol/L) were detected by CCK8 assay in KG1α and primary adult acute leukemia cells. Different concentrations of ITC for 7, 14 and 21 days were applied for observing the effect on colony formation. After 48 h treatments with 6 µmol/L ITC, 0.75 µmol/L ADM or ITC (6 µmol/L) plus ADM (0.75 µmol/L), the morphological changes of cells were observed by Wright staining. Flow cytometry was used to detect cell apoptotic rate, mitochondrial membrane potential and cell cycle arrest. And the expression levels of Sonic Hedgehog (Shh) signal pathway-related proteins Shh and glima-associated oncogene homdog1 (Gli1) were determined by Western blot. ITC and ADM inhibited the proliferation of KG1α and primary adult acute leukemia cells and ITC reduced the colony-formation ability of KG1α cells both in dose-dependent manners. Compared with control or single drug group, the changes of cell morphology were more apparent in combined group. Weeb coefficient test revealed a synergistic effect (D ≤ 70%C) of 0.75 µmol/L ADM plus 6 µmol/L ITC. When KG1α cells were treated with 6 µmol/L ITC plus 0.75 µmol/L ADM, the apoptotic rate was 31.72% ± 1.58%. And it was significantly higher than that in control, ITC and ADM groups (4.17% ± 0.74%, 4.33% ± 1.12%, 9.53% ± 1.15%, P < 0.01). Detection of mitochondrial membrane potential showed that low red-fluorescent cells (P3) of combined group were obviously higher than that in control, ADM and ITC single drug groups (18.80% ± 0.96% vs 5.00% ± 0.38%, 9.70% ± 0.43%, 7.10% ± 0.77%, P < 0.01) . KG1α cells were obviously arrested in G2 phase in combined group and it showed no statistical significance compared with control or single drug group. Western blot showed that the expression levels of Shh and Gli1 decreased with rising concentration of ITC. ITC plus ADM can obviously inhibit cell proliferation and increase KG1α cell apoptotic rate, mitochondrial damage and G2 phase retardation. And ITC inhibits the Shh signal pathways.

Multidrug Resistance (mdrl) Gene Expression in Adult Acute Leukemias: Correlations With Treatment Outcome and In Vitro Drug Sensitivity

Resistance to multiple chemotherapeutic agents has been related to the production of P-glycoprotein, a trans-membrane drug efflux pump that is encoded by the multidrug resistance (MDR) gene mdr1. To investigate whether mdr1 could be involved in clinical resistance to chemotherapy in acute leukemias, we have analyzed retrospectively the RNA from adult acute leukemia cells by slot-blot hybridization with a human mdr1 probe. Units of mdr1 expression were defined by reference to drug-sensitive human sarcoma and K562 leukemia cell lines (1 U) and the highly resistant doxorubicin selected leukemia cells K562/R7 (50 U). We studied 41 adult patients with acute leukemias: 5 acute lymphoblastic leukemias, 23 acute myeloid leukemias, and 13 secondary leukemias or blast crisis of chronic myelogenous leukemia. Expression of 10 U or more of mdr1 was found in 6 of 31 (19%) leukemias at diagnosis, versus 5 of 10 (50%) after relapse from therapy, P = .06. The complete remission rate and in vitro sensitivity to daunorubicin were both correlated with low expression (1 U, v 2 U or more) of mdr1. Among 36 evaluable attempts to induce remission, the complete remission rate was 67% (8 of 12) for patients with undetectable or minimal mdr1 expression (1 U), versus 29% (7 of 24) in patients with 2 U or more of expression, P = .03. In vitro resistance to daunorubicin or other MDR-related drugs was associated with expression of 2 U or more of mdr1 in 11 of 11 cases, while specimens that were sensitive to these agents were negative for mdr1 expression in 5 of 11 cases, P = .03. These data suggest that mdr1 expression contributes to chemoresistance in acute leukemia. Determination of mdr1 gene expression may be useful in designing therapy for patients with leukemia.

Multidrug resistance (mdr1) gene expression in adult acute leukemias: correlations with treatment outcome and in vitro drug sensitivity

Resistance to multiple chemotherapeutic agents has been related to the production of P-glycoprotein, a trans-membrane drug efflux pump that is encoded by the multidrug resistance (MDR) gene mdr1. To investigate whether mdr1 could be involved in clinical resistance to chemotherapy in acute leukemias, we have analyzed retrospectively the RNA from adult acute leukemia cells by slot-blot hybridization with a human mdr1 probe. Units of mdr1 expression were defined by reference to drug- sensitive human sarcoma and K562 leukemia cell lines (1 U) and the highly resistant doxorubicin selected leukemia cells K562/R7 (50 U). We studied 41 adult patients with acute leukemias: 5 acute lymphoblastic leukemias, 23 acute myeloid leukemias, and 13 secondary leukemias or blast crisis of chronic myelogenous leukemia. Expression of 10 U or more of mdr1 was found in 6 of 31 (19%) leukemias at diagnosis, versus 5 of 10 (50%) after relapse from therapy, P = .06. The complete remission rate and in vitro sensitivity to daunorubicin were both correlated with low expression (1 U, v 2 U or more) of mdr1. Among 36 evaluable attempts to induce remission, the complete remission rate was 67% (8 of 12) for patients with undetectable or minimal mdr1 expression (1 U), versus 29% (7 of 24) in patients with 2 U or more of expression, P = .03. In vitro resistance to daunorubicin or other MDR-related drugs was associated with expression of 2 U or more of mdr1 in 11 of 11 cases, while specimens that were sensitive to these agents were negative for mdr1 expression in 5 of 11 cases, P = .03. These data suggest that mdr1 expression contributes to chemoresistance in acute leukemia. Determination of mdr1 gene expression may be useful in designing therapy for patients with leukemia.

Surface Membrane Characteristics and Cytochemistry of the Abnormal Cells in Adult Acute Leukemia

Membrane marker and cytochemical analyses were carried out on the abnormal cells from 70 adult acute leukemia patients. Such information may (1) supplement standard morphology and serve as a basis for a new classification scheme for acute leukemia, and (2) characterize the surface membranes of granulocyte, lymphocyte, and monocyte "progenitors." Classification of acute lymphoid leukemias solely on the basis of morphology was unsatisfactory. The presence or absence of T- or B-cell markers was helful in classifying lymphoid leukemias. Monocyte progenitors were characteristically nonspecific esterase positive and Fc-receptor and membrane-IgG positive, but poorly phagocytic. Promyelocytes and myelocytes were frequently Fc-receptor positive and consequently positive for surface immunoglobulin. Myeloblasts were characteristically Fc-receptor negative. We conclude that surface membrane markers are essential in diagnosing lymphoid leukemias and helpful in nonlymphoid acute leukemias, and that cytochemistry is essential in delineating lymphoid from nonlymphoid leukemias and in subclassifying the latter.

Surface membrane characteristics and cytochemistry of the abnormal cells in adult acute leukemia

Membrane marker and cytochemical analyses were carried out on the abnormal cells from 70 adult acute leukemia patients. Such information may (1) supplement standard morphology and serve as a basis for a new classification scheme for acute leukemia, and (2) characterize the surface membranes of granulocyte, lymphocyte, and monocyte “progenitors.” Classification of acute lymphoid leukemias solely on the basis of morphology was unsatisfactory. The presence or absence of T-or B-cell markers was helful in classifying lymphoid leukemias. Monocyte progenitors were characteristically nonspecific esterase positive and Fc-receptor and membrane-IgG positive, but poorly phagocytic. Promyelocytes and myelocytes were frequently Fc-receptor positive and consequently positive for surface immunoglobulin. Myeloblasts were characteristically Fc-receptor negative. We conclude that surface membrane markers are essential in diagnosing lymphoid leukemias and helpful in nonlymphoid acute leukemias, and that cytochemistry is essential in delineating lymphoid from nonlymphoid leukemias and in subclassifying the latter.