Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With respect to the enzymes of NADPH-forming metabolic pathways in human leukocytes: (a) Glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase (decarboxylating) were less active in leukocytes (mostly myeloblasts) from eight patients with acute myeloblastic leukemia (I) than in leukocytes (mostly granulocytes) from 16 normal subjects (II). (b) Of the enzymes of the citrate cleavage pathway, ATP citrate lyase and malate dehydrogenase (decarboxylating) (NADP+) were virtually absent in the cells studied. (c) Isocitrate dehydrogenase (NADP+), aspartate aminotransferase, and alanine aminotransferase, which, together with the much more active malate dehydrogenase, constitute a newly proposed NADPH-forming metabolic cycle, showed a higher activity in I than in II or III, and therefore could compensate, as concerns NADPH-generation, for the low activity of pentose cycle dehydrogenases. We are not sure whether the enzymatic characteristic of I cells is attributable to their immaturity or to their leukemic nature.
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PMID:Enzyme activities of NADPH-forming metabolic pathways in normal and leukemic leukocytes. 23 46

The incorporation of 3H-leucine as an indicator of protein synthesis has been studied of blast cells in acute leukaemia and of proliferative normal bone marrow cells. The results demonstrate a significantly higher 3H-leucine incorporation into normal immature cells as compared to leukaemic myeloblasts, also 3H-leucine labelling of lymphoblasts was significantly lower than both the values found in acute leukaemia and normals. Higher protein synthesis was found correlated to the degree of cell immaturity. No significant correlation between 3H-leucine labelled and 3H-thymidine labelled leukaemic blast cells was achieved. A marked decrease in 3H-leucine incorporation by puromycin was demonstrated in three patients with acute myeloid leukaemia.
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PMID:Leucine incorporation into leukaemic blast cells. 29 96

This study is based upon an analysis of the hematologic and pathologic material from seven patients with acute myelosclerosis, as well as a review of the literature of 49 cases reported under this designation, or one of its synonyms. Patients with this disease characteristically present with pancytopenia, minimal or absent anisocytosis and poikilocytosis, and a fibrotic bone marrow showing hyperplasia and immaturity of all three cell lines, with particular prominence of megakaryocytes and their precursors. In addition, clinical splenomegaly is almost always absent, and the disease has a rapidly fatal course. We consider only one-fourth of the cases reported in the literature to have the clinical and hematologic features consistent with the diagnosis of acute myelosclerosis; the remainder represent a variety of myeloproliferative disorders, including chronic myelosclerosis with an accelerated terminal phase, acute myeloblastic leukemia with bone marrow fibrosis, myeloproliferative diseases that cannot be subclassified, and cases in which the data are insufficient for analysis. Using strict clinical and hematological criteria, acute myelosclerosis can be separated from other myeloproliferative disorders as a distinct clinicopathologic entity.
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PMID:Acute ("malignant") myelosclerosis. 36 69

With the aim of improving the treatment of AML patients the activities of selected nucleoside metabolizing enzymes of possible implication for the initial metabolism of Ara-C have been studied in leukemic and normal cells. An increased ADA activity, a slightly changed PNP activity, a decreased CDD activity and an increased dCK activity, including deviation in substrate specificity, were found in myeloid leukemic cells. The increase of ADA may in part be related to immaturity of the cells. This is supported by the finding of a decrease in the ADA activity during experimental induced differentiation of myeloid cells. On the other hand differentiation is not dependent on the ADA decrease, since differentiation can occur without the decrease of ADA. The correlation between myeloid blast counts in peripheral blood from AML patients and the ADA activity also supports the connection between the development stage of the cells and the ADA activity. Minor changes of the ADA activity in myeloid cells from patients with liver cirrhosis have been observed without changes in the maturity of the cells indicating that other factors than the differentiation of the cells are of importance for the activity of ADA in myeloid cells. Only minor changes have been observed in the activity of PNP related to myeloid leukemic cells. CDD activity is decreased in myeloid leukemic cells. Differentiation is probably of major importance for the activity, experimentally supported by the increase observed concurrently with induced differentiation of myeloid cells. An inverse correlation between the CDD activity and the blast counts in patients with AML is also supportive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Features of the initial metabolism of 1-beta-D-arabinofuranosylcytosine in human myeloid leukemic cells. 202 53

During the diagnostic investigation of 750 acute leukemias, nine cases were morphologically, cytochemically, and phenotypically undifferentiated. In seven of these cases the blasts were class II+, CD34+ and TdT+, in one were class II+, TdT+, CD7+ while in the remaining leukemia blasts expressed class II only. Cytoplasmic and membrane CD22, CD3, CD13, and Ig as well as membrane CD19, CD10, CD37, CD2, CD33, CD14, glycophorin C, and CD61 were absent. The further characterization of these rare leukemias yielded the following results. The TCR-beta, -gamma and -delta genes were in germline configuration in seven cases studied while IgH genes were rearranged on both alleles in two cases and germline in the other five. By ultrastructural analysis peroxidase activity was detected on unfixed cells in a minority of blasts from four of seven cases. In two of the peroxidase-positive cases a small proportion of blasts also reacted with an anti-myeloperoxidase monoclonal antibody. In one of the peroxidase-negative cases, 7% of blasts were labeled by the antibody, suggesting the presence of peroxidase in its proenzyme form. Importantly, the two cases with Ig gene rearrangements did not have cytochemically or immunologically detectable peroxidase. Three of the nine patients were treated as ALL while six received AML chemotherapy. In five patients complete remission was achieved while the other four died from infections during remission induction. Four patients are still in remission 7, 12, 24, and 30 months after diagnosis while one patient relapsed after 12 months. In conclusion, we have characterized the genotypic and ultrastructural features of subtype of acute leukemia in which blasts expressed immaturity markers and lacked lineage associated antigens. In contrast to previously reported "unclassifiable" cases, the leukemias were phenotypically homogeneous and showed a good response to chemotherapy.
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PMID:Phenotypic, genotypic, cytochemical, and ultrastructural characterization of acute undifferentiated leukemia. 239 82

Multiple monoclonal antibodies and enzyme assays were used to study maturity markers (myelo-peroxidase) and immaturity markers (terminal transferase, HLA-2) in acute myeloid leukemia cells from 35 patients. In 8 of the patients, indications were found of an expression of maturity and immaturity markers on the same cells, here in called maturation asynchrony. It is suggested that the orderly appearance and disappearance of markers during the maturation of normal cells is disordered in malignant cells, and that single markers should be used with caution for the maturation classification of tumors. The simultaneous expression of maturity and immaturity marker by tumor cells could explain also why such cells can be recognized as abnormal even in the absence of tumor specific antigens.
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PMID:Maturation asynchrony in leukemic cells. An abnormal combination of normal cell markers. 299 49

A case of lepromatous leprosy with erythema nodosum leprosum (ENL) presenting as a myeloid leukemoid reaction is reported. Very high leucocyte count with immaturity of the cells in myeloid series was present in peripheral blood. High leucocyte alkaline phosphatase score, absence of hepatosplenomegaly and transient nature of leukemoid reaction differentiated it from chronic myeloid leukemia and acute myeloblastic leukemia. The possible mechanisms of leukemoid reaction in ENL are discussed.
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PMID:Leukemoid reaction in erythema nodosum leprosum in a leprosy patient. 325 36

A total of 412 cases of acute leukaemia were examined for the presence of nuclear terminal deoxynucleotidyl transferase (TdT) by indirect immunofluorescence. Of the 129 cases of acute myeloblastic leukaemia (AML FAB groups M1/M2) examined, 18% (n = 23) had significant proportions (greater than 10%) of TdT-positive blasts. Although most of these AML cases (n = 18) were of poorly differentiated (M1) type; 5 cases of AML showing features of granulocytic differentiation (M2) were also found to be TdT-positive. Even though TdT was generally more strongly expressed in the M1 group and associated with other markers of myeloid immaturity (Ia positive and lack of chloroacetate esterase), there was no inverse relationship with Sudan black or myeloperoxidase activity. In addition, although the proportion of AML-M1 cases with increased TdT-positive cells was slightly higher (18/95, 19%) than for the AML-M2 group (5/34, 15%) the results suggest that the presence of nuclear TdT in leukaemic myeloblasts may not only reflect cellular immaturity but may also be due to maturational asynchrony in otherwise well-differentiated blasts.
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PMID:TdT expression in acute myeloid leukaemia. Haemopoietic immaturity or maturational asynchrony? 342 68

Six hundred and nineteen patients with de novo acute myeloid leukaemia, entered into the Medical Research Council's eighth trial of therapy have been studied. All patients were treated with the same remission induction regimen. Pretreatment variables comprising age, clinical status, haematological status and a detailed marrow cytology and cytochemistry score have been analysed. Poorer remission rates have been found in older patients, in those with lower Karnofsky scores and in patients with a platelet count of less than 25 X 10(9)/l. Leukaemias showing evidence of cytoplasmic maturation along the granulocyte and monocyte lines, as evidenced by granules, Auer rods, a high percentage of Sudan black positive blast cells and morphological and cytochemical abnormalities of neutrophils were associated with a higher remission rate. Marrow eosinophilia was a good prognostic feature. Nuclear features of immaturity, i.e. increasing numbers and prominence of nucleoli were associated with a low remission rate. Abnormalities of the erythroid series, notably Periodic acid-Schiff positivity which was present in 133 cases (22% of the total), was associated with a low remission rate. Patient age and pretreatment Karnofsky score were the most useful predictors of treatment outcome.
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PMID:Features affecting outcome during remission induction of acute myeloid leukaemia in 619 adult patients. 346 40

Leukaemia cell mobility was evaluated by the agarose plate method in 20 children with acute myeloid leukaemia (AML) based on the FAB classification. M1 blasts from 3 patients did not show any migration, probably reflecting their cellular immaturity. Leukaemia cells from 3 of 8 patients with M2 AML showed random migration, but those from the remaining 5 did not have this ability. The results thus demonstrated the heterogeneity of M2 AML in the function as well as the morphology. The M3 leukaemia cells failed to migrate under agarose in 2 patients studied, implying that a certain cytoskeletal defect in the cells. In all of 2 M4, 2 M5A and 3 M5B AML patients, leukaemia cells showed active mobility. The random migration value (mean +/- SD) of M5A and M5B cells was 5.7 +/- 1.7 compared with that of normal monocytes of 4.0 +/- 0.4 (p less than 0.01), indicating the enhanced random migration of leukaemia monocytes. M4 and M5B leukaemia cells had chemotactic responsiveness to zymosan-activated serum comparable to that of normal monocytes, but M5A cells were different from them in lacking apparent chemotactic responsiveness to the factor. Lymphadenopathy and leucocytosis were more prominent in the patients whose leukaemia cells were capable of migration than in those not having such cells. Mobility of leukaemia cells probably reflects their cell lineage, cellular maturity and functional distortion during leukaemic transformation, and appears to be related to clinical features.
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PMID:Leukaemia cell mobility in childhood acute myeloid leukaemia based on the FAB classification. 386 30


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