Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results of lymphocyte immunophenotyping in a variety of autoimmune disorders confirm major T cell immunoregulatory defects. The defects associated with autoreactive T cells appear to exist at the level/interface of the CD4 inducer of suppression and the CD8 effector cell. Although activated CD4 cells are occasionally found, subpopulations of activated CD8 cells are seen more commonly. A similar observation has been made in a subpopulation of patients with common variable hypogammaglobulinemia. In conjunction with antigen-specific T cell clones, we anticipate that flow cytometry will continue to aid in the further dissection of these HLA-restricted, anti-idiotype-controlled and pharmacological-mediated reactions. The known immunological distinction between AML and ALL are such that blast immunophenotyping will confirm and complement the clinical and morphological diagnosis in the vast majority of patients. With regards to chronic lymphocytosis in general and CLL in particular, flow cytometry offers an unusual opportunity to characterize lineage, monoclonality, stage of differentiation, presence or absence of activation antigens, aneuploidy and oncogene expression. Flow cytometry will continue to contribute to our understanding of the etiology and pathogenesis of CLL.
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PMID:Application of lymphocyte immunophenotyping in selected diseases. 306 65

Anti-CD3 (T3) Ab reacting with different proportions of thymocytes (anti-CD3a: UCHT1, anti-CD3b: T10B9, and anti-CD3c: OKT3) were tested for cytoplasmic (cCD3) and membrane (mCD3) expression in the bone marrow, thymus, and blood in man and selected primates. The expression of cCD3a and cCD3c in the perinuclear and Golgi area of large, BrdU-incorporating, strongly TdT+ thymic blasts probably represents one of the earliest signs of T cell commitment, because these blast cells are CD1-, CD4-, CD8-, and mCD3-. The cCD3+, TdT+ cells are normally restricted to the thymus and are absent among the TdT+ cells of bone marrow. The anti-CD3b Ab used, T10B9, co-caps and co-modulates with the other anti-CD3 Ab and is a T cell-specific reagent at a membrane level but does not bind to perinuclear cCD3. Instead, this reagent cross-reacts with a filamentous cytoplasmic network in non-T cells in man and in primates S. oedipus and M. rhesus despite their T cell negativity for mCD3. The characteristics of all T-ALL cases studied: cCD3+, CD7+ along with nuclear TdT+ suggest lineage fidelity to early thymic blasts. As a marked contrast, cCD3 is absent in common ALL and in AML, including cases that concomitantly express CD7 and myeloid antigens. Thus, the cCD3, TdT combination provides a very sensitive assay for residual T-ALL blasts outside the normal thymus.
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PMID:The cytoplasmic expression of CD3 antigens in normal and malignant cells of the T lymphoid lineage. 309 52

The lymphocyte subset reconstitution after high-dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation (ABMT) has been studied in ten patients with acute leukemia (AL) (6 ALL and 4 ANLL) in complete remission (CR). Bone marrow was treated in vitro with high-dose ASTA Z 7557, individually determined according to CFU-GM sensitivity. The different peripheral blood lymphocyte subsets were characterized by means of monoclonal antibodies (indirect immunofluorescence assay) belonging to the following classes of differentiation: OKT11-T11 (CD2), OKT3-T3 (CD3), OKT4-T4 (CD4), OKT8-T8 (CD8), OKIal-I2 (HLA-DR), Leu7 (natural killer/killer) and by means of polyspecific antiimmunoglobulin sera (direct immunofluorescence assay). Data in these ten patients were compared with those of a control group of 21 normal donors and with a control group of 14 patients in CR without ABMT. Our results showed a marked depression of the T4:T8 ratio in patients with AL before ABMT, compared with normal donors who had respective values of 1.02 and 1.33 (p less than 0.01). This depression was increased and prolonged up to day 515 after ABMT, with a value of 0.32 (p less than 0.01 compared with the pregraft situation; p less than 0.001 compared with normal donors). This T4:T8 ratio imbalance was related to the depletion of the T4+ population and to the increase of the T8+ subset. This imbalance was emphasized after ABMT. The Leu 7+ population was also increased in grafted patients compared with normal donors (p less than 0.01). The B-cell population remained unchanged throughout the study. We conclude that patients autografted with marrow treated in vitro by high-dose ASTA Z 7557 may experience a long-term T-cell subset imbalance.
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PMID:Evaluation of lymphocyte subsets after autologous bone marrow transplantation with marrow treated by ASTA Z 7557 in acute leukemia: incidence of the in vitro treatment. 351 64

In the past, studies on CD34+ cells have been based on the use of monoclonal antibodies conjugated with different fluorochromes that show different fluorescence intensity and yield variable results. Moreover, most of these studies have neither specifically focused on adult human BM samples nor have they used combinations to explore specifically the phenotype of myeloid committed CD34+ cells. The aim of the present study has been to characterize the normal human CD34+ precursor cells from adult BM in order to identify missing or extremely rare phenotypes that can be used for detecting minimal residual disease (MRD) in patients with AML. For this purpose we have utilized the fluorochrome conjugates that provide the most sensitive signals for identifying low antigenic expression, and the technique has been adapted to the characterization of cells present at very low frequencies. Normal human BM samples from 13 adult healthy volunteers have been analyzed using triple stainings at flow cytometry. The mean percentage of CD34+ cells detected was 0.72 +/- 0.33%; these cells displayed an heterogeneous light-scatter distribution. Most CD34+ cells coexpressed CD38 (96.7 +/- 5.7%), HLADR (81.6 +/- 14.0%), CD33 (84.7 +/- 18.3%), CD13 (84.6 +/- 16.2%) and CD71 antigens (65.5 +/- 9.1%). In addition, almost half of CD34+ cells were CD117+ (60 +/- 26.8%). Only a small proportion of CD34+ cells coexpressed CD4 (15.5 +/- 11.7%, CD36 (31.7 +/- 6.2%), CD61 (16.3 +/- 12.9%), CD41 (6.5 +/- 5.5%) or the lymphoid associated markers CD10 (18.6 +/- 11.8%) and CD19 (12.3 +/- 13.2%). Reactivity for the CD15 antigen was observed in a small population of CD34+HLADR+ cells (11.6 +/- 11.2%) although its intensity of expression was lower than that of the more mature granulocytic cells. No CD34+ cells displayed CD14, CD65, CD20, strong CD22, CD3 and CD56 antigens. Accordingly, most adult bone marrow CD34+ cells appeared to be committed to the myeloid lineage (CD13+/CD33+) and displayed an intermediate-to-large FSC/SSC while the lymphoid-committed CD34+ cells (CD19+, CD10+) were in a minority with low FSC/SSC values. By triple marker stainings several phenotypes of CD34+ precursor cells were found to be either undetectable or present at very low frequencies (< 1 x 10(-3)) in the normal human adult bone marrow. These data may be of great value for defining leukemia 'associated' phenotypes used to detect minimal residual disease in adult acute leukemia patients.
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PMID:Phenotypic analysis of CD34 subpopulations in normal human bone marrow and its application for the detection of minimal residual disease. 747 81

In the present study, the expression of two NK-associated antigens (CD56 and CD16) together with six 'classically' considered lymphoid-related markers (TDT,CD19,CD10,CD7,CD2,CD4) has been analyzed by appropriate dual combinations in 265 acute myelogenous leukemia (AML) patients. Among the lymphoid markers, CD4 and CD7 were those most frequently expressed by AML blast cells (58% and 21.6%, respectively) while the incidence of positivity for the other markers was lower: CD19 (7.8%), CD10 (10.9%), CD2 (11.4%), and TDT (11.3%). Regarding NK-associated antigens, CD56 was present in 41% of AML cases analyzed whereas CD16 was detected in only 23%. All but one of the CD16+ cases coexpressed the CD56 antigen. The expression of these antigens was not associated with the degree of cell differentiation assessed either by morphological or immunophenotypical criteria, with the exception of the correlation observed between monocytic leukaemias and the expression of the CD4, CD56, and CD16 antigens. Regarding the prognostic value of the markers investigated, CD56 expression was associated with a tendency for a better outcome whereas CD7 was the only antigen that had an adverse influence on the survival of AML patients.
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PMID:Expression of NK and lymphoid-associated antigens in blast cells of acute myeloblastic leukemia. 750 72

A 75-year-old man developed a cluster of differentiation (CD)4-positive but human T-cell lymphotropic virus type I (HTLV-I)-negative T lymphoid neoplasm with overwhelming cutaneous involvement and mild thrombocytosis. Twelve courses tetrahydropyranyl adriamycin, cyclophosphamide, vincristine and prednisone (THP-COP) combination chemotherapy led him to complete remission. After four months of complete remission, however, atypical immature cells (blasts) appeared in peripheral blood and bone marrow. Surface marker analysis revealed the blasts to be CD2-, CD3-, CD4-, CD5-, CD7+, CD8-, CD10, CD13 +/-, CD19-, CD20-, CD25-, CD33+ and human leukocyte antigen-DR (HLA-DR+). Staining for myeloperoxidase, esterases, PAS and platelet peroxidase were all negative. The patient was diagnosed as having both CD7 and CD33 positive acute myeloid leukemia (AML). The relation between the T cell lymphoid neoplasm and AML was not clear. Thrombocytosis became more marked after acute leukemia occurred and the platelet count varied in parallel with the blast cell count in peripheral blood. When the leukemic cell count was high, thrombopoietic activity could be detected in the serum. In addition, conditioned medium obtained from primarily-cultured blasts had detectable thrombopoietic activity, which implied the blasts directly to produce a thrombopoietic factor(s). Analysis of the serum concentration for cytokines with associated thrombopoietic activity indicated that the blasts possibly produced a thrombopoietic factor(s) distinct from interleukin (IL)6, IL3, leukemia inhibitory factor (LIF), erythropoietin and granulocyte macrophage-colony stimulating factor. To our knowledge, this is the first reported case of an acute myeloid leukemia with marked thrombopoiesis (more than 2000 x 10(3)/microliter of maximum platelet count in peripheral blood.
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PMID:Acute myeloid leukemia possibly producing thrombopoietic factor(s). 750 2

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

We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both myeloid and natural killer (NK) cells. From a consecutive series of 350 cases of adult de novo acute myeloid leukemia (AML), we identified 20 cases (6%) with a unique immunophenotype: CD33+, CD56+, CD11a+, CD13lo, CD15lo, CD34+/-, HLA-DR-, CD16-. Multicolor flow cytometric assays confirmed the coexpression of myeloid (CD33, CD13, CD15) and NK cell-associated (CD56) antigens in each case, whereas reverse transcription polymerase chain reaction (RT-PCR) assays confirmed the identity of CD56 (neural cell adhesion molecule) in leukemic blasts. Although two cases expressed CD4, no case expressed CD2, CD3, or CD8 and no case showed clonal rearrangement of genes encoding the T-cell receptor (TCR beta, gamma, delta). Leukemic blasts in the majority of cases shared unique morphologic features (deeply invaginated nuclear membranes, scant cytoplasm with fine azurophilic granularity, and finely granular Sudan black B and myeloperoxidase cytochemical reactivity) that were remarkably similar to those of acute promyelocytic leukemia (APL); particularly the microgranular variant (FAB AML-M3v). However, all 20 cases lacked the t(15;17) and 17 cases tested lacked the promyelocytic/retinoic acid receptor alpha (RAR alpha) fusion transcript in RT-PCR assays; 12 cases had 46,XX or 46,XY karyotypes, whereas 2 cases had abnormalities of chromosome 17q: 1 with del(17)(q25) and the other with t(11;17)(q23;q21) and the promyelocytic leukemia zinc finger/RAR alpha fusion transcript. All cases tested (6/20), including the case with t(11;17), failed to differentiate in vitro in response to all-trans retinoic acid (ATRA), suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA. Four of 6 cases tested showed functional NK cell-mediated cytotoxicity, suggesting a relationship between these unique CD33+, CD56+, CD16- acute leukemias and normal CD56+, CD16- NK precursor cells. Using a combination of panning and multiparameter flow cytometric sorting, we identified a normal CD56+, CD33+, CD16- counterpart cell at a frequency of 1% to 2% in the peripheral blood of healthy individuals. Our studies suggest that this form of acute leukemia may arise from transformation of a precursor cell common to both the myeloid and NK cell lineages; thus we propose the designation myeloid/NK acute leukemia. Recognition of this new leukemic entity will be important in distinguishing these ATRA-nonresponsive cases from ATRA-responsive true APL.
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PMID:HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3. 752 45

The classification of acute leukemia into lymphoid or nonlymphoid is of critical therapeutic importance. Two-color flow cytometric analysis has emerged as a valuable addition to morphology and cytochemistry for the distinction of acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL). By careful selection of monoclonal antibody (mAb) combinations, diagnostic accuracy, and cost effectiveness may be enhanced compared to flow cytometry using one-color analysis. The sensitivity and specificity of a mAb panel were assessed in the determination of nonlymphocytic lineage in acute leukemia. One hundred twenty-five consecutive cases of acute leukemia were analyzed in which Wright's-stained smears, cytochemical stains, and immunophenotyping studies had been performed. The antibody panel included the nonlymphoid markers CD13, CD33, CD14, and CD4 in combination with CD2, as well as a broad panel of lymphoid and nonlineage specific markers. Of the 125 cases of acute leukemia studied, 85 cases (68%) were nonlymphocytic and 32 cases (26%) were lymphocytic (28 cases B cell, 4 cases T cell). CD13 and CD33 were very sensitive in the detection of ANLL, being expressed on 94% and 93% of ANLL cases, respectively. Sixty-five percent of cases of ANLL were CD4+ (CD2-). However, CD4+ (CD2-) had a much higher specificity (91%) for ANLL than CD13 (75%) or CD33 (84%), which were expressed in a significant number of ALL. When leukemic cells were positive for CD4 (CD2-) and either CD13 or CD33, specificity and positive predictive value (PPV) for ANLL rose to 96% and 98%, respectively. The combination of CD4 positivity with either CD13 or CD33 has higher specificity and PPV than the traditional positivity for both CD13 and CD33 (specificity 89%, PPV 96%). Careful analysis of the sensitivity, specificity, and predictive values of mAbs using this method has also allowed us to establish a more cost-effective and diagnostically relevant mAb panel. Our studies show that CD4 is underappreciated as a very specific and moderately sensitive marker for ANLL.
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PMID:CD4 predicts nonlymphocytic lineage in acute leukemia. Insights from analysis of 125 cases using two-color flow cytometry. 938 55

Fourteen cases of lymphoid and myeloid acute leukemia (AL) were studied for expression on blast cells of CD7 antigen, a cell surface marker found early during T lineage differentiation. This heterogenic group of CD7+ CD4-CD8- AL includes distinct cytological subvariants with: myeloid (AML MO, M1, M4, M5) and lymphoid (pre-T-cell) commitment, biphenotypic or mixed lineage AL and AL with minimal signs of blast cell differentiation, which appear not to follow lineage restriction. The latter subset of AL may represent the transformed counterpart of an early stem cell prior to lineage commitment.
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PMID:[Immunophenotypic heterogeneity of CD7+CD4-CD8--acute leukemia]. 755 27


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