Prognostic implications of cytology in acute leukemia in the adultThe case for subacute leukemia
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Acute myelomonocytic leukemia
Acute lymphocytic leukemia
Objective To study the characteristic of immunophenotyping expressions of acute leukemia and the diagnostic value of that. Methods 282 cases of acute leukemia were detected by flow cytometry. three color direct immunofluo-rescence staining methods being used. And the antibody integration system was used to classify acute leukemia. Results Acute leukemia were classified into 4 subgruops:monophenotypic acute leukemia,acute leukemia which mainly expressed one lineage-specific antigens,hybrid acute leukemia (HAL) and acute undifferentiated leukemia (AUL). And the percentages of them were 82. 27%,9. 22%,7. 09% and 1. 72% respectively. More than 80% of acute nonlymphocytic leukemias (ANLL) expressed MPO,CD13 and CD33. And more than 90% of acute lymphocytic leukemias (ALL) expressed cCD79a, CD19 or cCD3,CD2. Most of acute leukemias which mainly expressed one lineage-specific antigens were acute B lymphocytic leukemia with expression of myeloid antigen. And most of HAL were acute B lymphocytic leukemia and acute myeloid leukemia. Conclusion cCD3,cCD79a and MPO are lineage-specific antigens,and CD117 is prophase myeloid antigen. And they are important in diagnosis,classification,treatment and prognosis of acute leukemia.
Immunophenotyping
Acute lymphocytic leukemia
CD117
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Cytogenetic studies, using improved short-term culture techniques, were performed on 64 patients with acute leukemia to determine the incidence and kinds of clonal karyotypic changes detectable with this newer methodology. An adequate number of analyzable mitoses was obtained from 59 patients. Clonal chromosomal alterations were found in 88% (52 of 59) of patients, as compared to approximately 50% in previous studies of acute leukemia in which conventional techniques were used. From our series, abnormal karyotypes were detected in 37 of 44 (84%) cases with primary acute nonlymphocytic leukemia, all 5 with secondary acute nonlymphocytic leukemia, and all 10 with acute lymphoblastic leukemia. Among the entire group of patients, several recurrent abnormalities were observed, e.g., -7 in eight cases, +8 in seven cases, t(15;17) in four cases, and t(8;21) or a variant of this translocation in four cases. In five patients, the only abnormality was a rather subtle structural rearrangement (e.g., tiny deletion). Five other patients had clonal changes which were found in less than 10% of the mitoses examined in each case. Our results indicate that most patients with acute leukemia, both acute nonlymphocytic leukemia and acute lymphoblastic leukemia, have clonal chromosome abnormalities associated with their disease.
Acute lymphocytic leukemia
Abnormality
Chromosome abnormality
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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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Thirteen previously untreated patients aged 70 and above with acute nonlymphocytic leukemia were treated with aclarubicin (ACR) alone. Among 10 cases (3, acute myelocytic leukemia; 4, acute myelomonocytic leukemia; 2, acute monocytic leukemia; and one, acute erythroleukemia) in which an evaluation was possible, 5 cases (3, acute myelomonocytic leukemia; and 2, acute monocytic leukemia) obtained complete remission (CR). The CR rate was 83% in 6 patients with acute myelomonocytic leukemia or acute monocytic leukemia. The median CR duration and survival was 7.5 and 10 + months, respectively. Although side effects of the drug on digestive system such as nausea, vomiting and anorexia were observed in all patients, they were controllable by conventional treatments. The results suggest that ACR is effective for the clinical management of elderly patients with acute nonlymphocytic leukemia, especially those with acute myelomonocytic leukemia or acute monocytic leukemia.
Acute monocytic leukemia
Aclarubicin
Acute myelomonocytic leukemia
Monocytic leukemia
Monocytosis
Anorexia
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Acute leukemia associated with the t(4;11)(q21;q23) abnormality demonstrates marked lineage heterogeneity, including cases with features of acute mixed lineage leukemia. We report 7 patients with acute leukemia with the t(4;11) abnormality in which we have defined the range of lineage commitment associated with this disease utilizing a variety of cell characterization techniques. Each case could be classified either as acute lymphoblastic leukemia (ALL) (5 cases) or acute myelogenous leukemia (AML) (2 cases) based on standard light microscopic criteria supplemented by ultrastructural determination of myeloperoxidase. Evidence for acute mixed lineage leukemia was found in one of the AML patients in which coexpression of CD14 and CD19 surface antigens was demonstrated. Overall, the findings further confirm the lineage heterogeneity previously reported in association with t(4;11) acute leukemia. The implications of the findings as to the pathogenesis of t(4;11) acute leukemia are discussed.
Lineage (genetic)
Acute lymphocytic 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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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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Acute myelomonocytic leukemia
Acute lymphocytic leukemia
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Summary Introduction While the presence of disseminated intravascular coagulation ( DIC ) has been implicated in worse clinical outcome in acute leukemia, the relationship between different subtypes of acute leukemia and the clinicopathologic features of DIC has not been systematically well studied. Methods In this study, we retrospectively reviewed 149 cases of newly diagnosed acute leukemia and assessed the utility of evaluating red blood cell morphologic features, and coagulation parameters in determining the presence of DIC as well as differentiating subtypes of acute leukemia. Results Review of our cohort demonstrates a novel finding, that elevated D‐dimer concentrations ≥19 000 ng/ mL fibrinogen equivalent units ( FEU ) are a sensitive diagnostic indicator of acute promyelocytic leukemia ( APL ) with moderate specificity, sensitivity 96%, specificity 92% in acute leukemia subtyping. Similar to other studies, APL showed an increased incidence of DIC ( P < 0.01) compared to other subtypes of acute leukemia. Surprisingly, the presence of schistocytes on the peripheral blood smear was not a statistically significant indicator of DIC , sensitivity of 36% and specificity of 89%. Finally, the presence of DIC was not a significant indicator of poorer prognosis amongst all patients with AML . Conclusion Overall we identify elevated D‐dimer concentrations ≥19 000 ng/ mL FEU are a sensitive indicator of acute promyelocytic leukemia ( APL ), with a sensitivity of 96% and specificity of 92% in the subtyping of acute leukemias, and that the presence of schistocytes in peripheral blood smears is not a diagnostically sensitive screening test for DIC with a sensitivity of 36%.
D-dimer
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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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