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

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

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

A quantitative cytochemical study has been made, using scanning-integrating microdensitometry, of 1000 toxic granulation blood neutrophils from 20 infected patients, in comparison with 1250 normal blood neutrophils. Myeloid precursor cells in 10 normal marrows were also studied. Normal bone marrow granulocyte maturation was associated with a progressive decrease in azurophilic granule enzymes (myeloperoxidase, beta-glucuronidase, acid phosphatase, chloroacetate esterase), and also Alcian blue staining from acid mucosubstance, but an increase in the specific granule marker lactoferrin. Toxic granulation blood neutrophils showed minor changes in the enzyme content of their azurophilic and specific granules, consistent with cell immaturity, and an increase in acid mucosubstance in azurophilic granules. Abnormal maturation of azurophilic granules, with persistence of acid mucosubstance, is the likely explanation for the intense Romanowsky dye staining of the toxic granulation neutrophil.
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PMID:Quantitative cytochemistry of the toxic granulation blood neutrophil. 684 17

The gene expression of myeloperoxidase (MPO), CD3 epsilon, and CD3 delta molecules, the gene rearrangement of T-cell receptor (TCR) delta, gamma, and beta and immunoglobulin heavy (IgH) chain, and the expression of cell-surface antigens were investigated in seven cases of CD7+ CD5- CD2- and four cases of CD7+ CD5+ CD2- acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LBL) blasts, which were negative for cytochemical myeloperoxidase (cyMPO). More mature T-lineage blasts were also investigated in a comparative manner. In conclusion, the CD7+ CD5- CD2- blasts included four categories: undifferentiated blasts without lineage commitment, T-lineage blasts, T-/myeloid lineage blasts, and cyMPO-negative myeloblasts. The CD7+ CD5+ CD2- blasts included two categories; T-lineage and T-/myeloid lineage blasts. The 11 cases were of the germ-line gene (G) for TCR beta and IgH. Four cases were G for TCR delta and TCR gamma. The others were of the monoclonally rearranged gene (R) for TCR delta and G for TCR gamma or R for both TCR delta and TCR gamma. The expression or in vitro induction of CD13 and/or CD33 antigens correlated with the immaturity of these neoplastic T cells, since it was observed in all 11 CD7+ CD5- CD2- and CD7+ CD5+ CD2-, and some CD7+ CD5+ CD2+ (CD3- CD4- CD8-) cases, but not in CD3 +/- CD4+ CD8+ or CD3+ CD4+ CD8- cases. CD3 epsilon mRNA, but not CD3 delta mRNA, was detected in two CD7+ CD5- CD2- cases, while mRNA of neither of the two CD3 molecules was detected in the other tested CD7+ CD5- CD2- cases. In contrast, mRNA of both CD3 epsilon and CD3 delta were detected in all CD7+ CD5+ CD2- cases, indicating that CD7+ CD5- CD2- blasts at least belong to T-lineage. The blasts of two CD7+ CD5- CD2- cases with entire germ-line genes and without mRNA of the three molecules (MPO, CD3 epsilon, and CD3 delta) were regarded as being at an undifferentiated stage prior to their commitment to either T- or myeloid-lineage. The co-expression of the genes of MPO and CD3 epsilon in a CD7+ CD5- CD2- case MPO, CD3 epsilon, and CD3 delta in a CD7+ CD5+ CD2- case suggested the presence of some overlapping phase for T- and myeloid-lineage commitment during immature stages of differentiation. This helps understand the conversion of some T-ALL/LBL cases to acute myeloblastic leukemia (AML).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lineage determination of CD7+ CD5- CD2- and CD7+ CD5+ CD2- lymphoblasts: studies on phenotype, genotype, and gene expression of myeloperoxidase, CD3 epsilon, and CD3 delta. 751 45

A 51-year-old man had suffered from massive pleural effusion due to invasion of malignant cells. The analysis of bone marrow aspiration showed the proliferation of myeloperoxidase-positive blasts. The surface marker analysis of the blasts revealed the positivities for CD7 and CD19 as well as CD13, CD33 and CD34, while the karyotypes of 20 cells were normal. Therefore, CD7 positive AML was diagnosed. The patient was treated with araC and daunorubicin as a remission induction therapy. Peripheral blood stem cells were harvested by leukapheresis after first and second consolidation therapies. Then, 3 x 10(4) cells/kg of CFU-GM were infused. Complete remission has been maintained for 8 months after autologous blood stem cell transplantation. Pleural involvement as an initial manifestation is rare in AML. Extramedullary growth of AML cells may be related to their immaturity, indicated by the expression of the cell surface antigens.
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PMID:[CD7 positive acute myelogenous leukemia exhibiting pleural involvement as an initial manifestation]. 752 3

Reports of treatment of patients with minimally differentiated acute myeloid leukemia (AML-M0) are limited, heterogeneous, and controversial. We verified the prognosis of this subtype by analyzing the results of 189 consecutive patients with de novo AML. Fifteen cases fitting the criteria of AML-M0 were identified. No clinical features distinguished them from other patients with AML. The median age was 61 years (range 27 to 70), with a leukocyte count ranging from 0.6 to 185 x 10(9)/L. In all cases the leukemic cells expressed CD34 and reacted with at least one of the antibodies to early myeloid antigens, ie, CD13, CD33, or myeloperoxidase. Immunophenotypic analysis also showed positivity for CD7 in seven samples and the multidrug-resistance P-glycoprotein (P-170) in six. Cytogenetic analysis was abnormal in 12 of the 13 patients in whom an adequate number of mitoses could be evaluated. No single abnormality prevailed, the most common findings being trisomy 8 (three cases) and aberrations of chromosome 7 (two cases). Antileukemic treatment differed according to age, but for remission induction, all patients received a combination of cytosine arabinoside and an anthracycline or mitoxantrone. The prognosis of patients with AML-M0 was remarkably poor as compared with the other French-American-British subtypes. Whereas the overall rate of complete remission (CR) was 58% with a median survival of 63 weeks, only 6 of the 15 patients with AML-M0 achieved a CR, and the median survival of this group was 16 weeks (range 3 to 39). The major determinant of treatment failure was unresponsiveness to chemotherapy, as only one patient died of infection during the hypoplastic phase. The CR duration of responders was short, ranging from 3 to 22 weeks, and no second remissions were observed. We conclude that conventional combination chemotherapy yields disappointing results in AML-M0. The reason for this may be the convergence of various unfavorable prognostic factors, such as (1) the high incidence of cytogenetic abnormalities; (2) the lack of differentiation features and the expression of immaturity markers such as CD34 and CD7; and (3) the frequent expression of P-170. Nonconventional therapeutic approaches should be developed to alter the prognosis of this form of leukemia.
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PMID:Analysis of treatment failure in patients with minimally differentiated acute myeloid leukemia (AML-M0). 812 53

Recent evidence has suggested that the immaturity of the neonatal intestine may play a key role in the development of ischemic injury. However, relatively little data exist on the susceptibility of the neonatal intestine to ischemic injury at various ages especially in the fed versus fasted states. In this study, the levels of xanthine oxidase ([XO] an enzyme which is a known, major source of free radicals in postischemic tissue) and myeloperoxidase ([MPO] an index of tissue neutrophil infiltration) were measured in 1-, 5-, 10-, 15-, and 20-day-old Sprague-Dawley rats. Rats were divided into fed (n = 8/day) and fasted (n = 8/day) groups 4 hours prior to sacrifice. The entire small intestine was removed and divided into five segments: the duodenum, proximal jejunum, distal jejunum, proximal ileum, and distal ileum. The specimens were homogenized and assayed for XO and MPO levels. A significant increase in XO was observed in the fasted animals compared to the fed animals on all days. Peak levels in XO were observed in both groups from day 5 to 10. MPO levels were significantly higher in the fasted versus fed animals on day 1. MPO levels decreased as the animals aged. These data demonstrate dramatic differences in the levels of inflammatory enzymes of the newborn rat in the fed versus fasted states. Also, marked variations with age are seen in both XO and MPO. Whether the XO and MPO levels present at the time of ischemic insult affect severity of injury remains to be seen.
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PMID:Inflammatory enzyme composition of the neonatal rat intestine: implications for susceptibility to ischemia. 839 43

The Bayer-Technicon hematological devices differentiate leukocytes by their peroxidase activity and their volume, displaying them as separate clusters. Peroxidase deficiencies are manifested by the irregular location of these clusters. This makes it possible to identify persons totally or partially lacking myeloperoxidase. The deficiency is quantified by the myeloperoxidase index, which is expressed for every routine analysis and for which normal values were determined. Values of the myeloperoxidase index confirm varying degrees of deficiency and prevalence. Family studies using these degrees show that the hereditary pattern must be more complicated than the classical autosomal-recessive mode. A bigenic mode is suggested. While about half of the totally deficient individuals detected were free of typical symptoms, in the other half we found infectious complications that were sometimes life-threatening. The hematological devices allow the identification of persons suffering from eosinoperoxidase deficiency and from MPO deficiency of the monocytes. The latter symptom seems to indicate immaturity of these cells and may lead to unexpected diagnosis of malignancy.
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PMID:Prevalence of myeloperoxidase deficiency: population studies using Bayer-Technicon automated hematology. 976 44

Knowledge of the blast phenotype in myelodysplastic syndrome (MDS) would be valuable, as in other malignancies, but remains sparse. This is mainly because MDS blasts are a minor population in clinical samples, making analysis difficult. Thus, for this blast phenotype study, we prepared blast-rich specimens (using a new density centrifugation reagent for harvesting blasts) from blood and marrow samples of 95 patients with various MDS subtypes and 21 patients with acute leukemia transformed from MDS (AL-MDS). Flow cytometry revealed that a high proportion of the enriched blast cells (EBCs) from almost all patients showed an immunophenotype of committed myeloid precursors (CD34(+)CD38(+)HLA-DR(+)CD13(+)CD33(+)), regardless of the disease subtype. The cytochemical reaction for myeloperoxidase was negative in 58% of the cases. Thus, the EBC phenotype is more immature in MDS than in de novo acute myeloid leukemia. MDS EBCs often coexpressed stem cell antigens and late-stage myeloid antigens asynchronously, but rarely expressed T- and B-lymphoid cell-specific antigens. Markers for myeloid cell maturation (CD10 and CD15) were more prevalent on EBCs from low-risk MDS (refractory anemia [RA] and RA with ringed sideroblasts), whereas markers for myeloid cell immaturity (CD7 and CD117) were more prevalent on EBCs from high-risk MDS (chronic myelomonocytic leukemia, RA with excess blasts [RAEB], and RAEB in transformation) and AL-MDS. A shift to a more immature phenotype of EBCs, accompanying disease progression, was also documented by sequential phenotyping of the same patients. Further, CD7 positivity of EBCs was an independent variable for a poor prognosis in MDS. These data represent new, valuable information regarding MDS.
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PMID:Clinical significance of phenotypic features of blasts in patients with myelodysplastic syndrome. 1239 41

Spleen is a common site of extramedullary hematopoiesis. Extramedullary hematopoiesis seen in non-neoplastic conditions can occasionally be extensive and raise concerns for a myeloid neoplasm. We compared the morphologic and immunohistochemical features of splenic hematopoietic proliferations seen in neoplastic myeloid disorders (eg chronic myeloproliferative disorders, myelodysplastic/myeloproliferative disorders and acute myeloid leukemias) to extramedullary hematopoiesis seen in a variety of reactive conditions. In all, 80 spleen specimens were reviewed. The presence of each marrow-derived lineage, dysplasia and immunohistochemical results were evaluated (CD34, CD117, myeloperoxidase, CD68, p53, TdT, CD42b and hemoglobin). Neoplastic hematopoietic proliferations in chronic myeloproliferative disorders are characterized by trilineage hematopoiesis with significant dysplasia in all cell lineages. Acute myeloid leukemia showed an increase in immature forms, which were highlighted by immunohistochemistry. Reactive extramedullary hematopoiesis showed variability in histologic features. Post-bone marrow transplant and thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome spleens showed extramedullary hematopoiesis with some morphologic features of immaturity, which could simulate chronic myeloproliferative disorder. However, they lacked characteristic immunohistochemical features of neoplastic myeloid disorders such as positivity for CD34 or CD117.
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PMID:Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders. 1611 26


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