Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NB91 (FAB)
 3,573 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whereas the diagnosis of acute lymphoid leukaemia greatly depends on immunophenotyping on the leukaemic cells, the diagnosis of acute myeloid leukaemia (AML) is still only based on morphological and cytochemical criteria. Here we describe that with a monoclonal antibody, directed against myeloperoxidase (MPO), the immunological diagnosis of AML is possible in most cases. A monoclonal antibody against lactoferrin (LF) was used to detect more mature myeloperoxidase-containing cells. Of the cell samples tested from 206 different patients with AML, 95% were found to express myeloperoxidase in more than 15% of lactoferrin-negative cells. Compared with other myeloid-reactive monoclonal antibodies (VIM2, anti-CD13, anti-CD14, anti-CD15 and anti-CD33), a higher diagnostic sensitivity and specificity for AML was found. No significant correlation with the FAB classification was found. In most patients, more MPO-positive cells were detected by the monoclonal antibody than by the cytochemical staining. This could be due to the recognition of enzymatically inactive precursor forms of myeloperoxidase by the antibody. The use of anti-myeloperoxidase monoclonal antibodies for the diagnosis of AML has the advantage that objective quantification is possible.
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PMID:Monoclonal antibodies against myeloperoxidase are valuable immunological reagents for the diagnosis of acute myeloid leukaemia. 216 59

The occurrence of immunoglobulin heavy chain (IgH) and/or T-cell receptor (TcR) gene rearrangements has been reported in some cases of acute non lymphoid leukemia (ANLL), and variously interpreted as reflecting "aberrant gene expression" or "lineage promiscuity" of the leukemic cell. In an attempt to verify the incidence, FAB distribution and immunophenotypic correlates of gene rearrangements in ANLL, we analyzed the configuration of IgH and TcR beta chain genes in 70 patients with ANLL. In all cases myeloid (CD13, CD33, CD14, CD15) and lymphoid (CD7, CD2, CD10, CD19, TdT) antigenic determinants were analyzed in conjunction with conventional morpho-cytochemical characterization. Clonal rearrangements of the IgH gene were identified in 6/70 ANLL patients (8.6%), whereas in only 2/48 (4.2%) were T beta rearrangements documented. Concerning FAB subtypes, IgH or T beta rearrangements were detected in the less differentiated forms MO and M1 (3 cases), as well as in 2 M4 and 1 M5a cases. With the exception of a higher incidence of gene rearrangements in TdT+ ANLL, no significant correlation was found with other immunophenotypic markers.
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PMID:Immunoglobulin heavy chain and T-cell receptor beta chain gene rearrangements in acute non lymphoid leukemia. 216

A study of surface markers and in vitro growth in semi-solid and liquid medium was performed in 35 patients with newly diagnosed myelodysplastic syndrome (MDS). Surface markers were studied by CD34, CD13, CD14, CD15, and CD33 monoclonal antibodies. There was no strict correlation with the FAB typing, but CD34 was expressed only in refractory anemia with excess of blasts (RAEB) or RAEB in transformation (RAEB-t). CD14 was markedly positive in the 4 cases of chronic myelomonocytic leukemia. Colony-forming cells were assessed by culture in semi-solid medium in the presence of HTB9 as growth factor. Four growth patterns were identified: a) normal growth (6 cases); b) no growth or low plating efficiency (10 cases); c) low colony and high cluster number (15 cases); and d) normal or high colony number with high number of clusters (4 cases). Expression of CD34 was associated with low colony and high cluster number. Finally we studied the proliferation and differentiation capacities in liquid culture without stimulating factor. Fifteen patients had a spontaneous proliferation. This was not correlated with any surface marker. Differentiation assessed by the loss of CD34 and/or the increase of CD15 by more than 20% at day 7 was observed in 21 cases. None of the surface markers or growth patterns was associated with a specific chromosomal abnormality, except the lack of growth in liquid culture observed in all 5q deletion cases. In univariate analysis, RAEB and RAEB-t FAB subtypes, percentage of blasts higher than 5%, staining by CD33 and CD34, and lack of differentiation in liquid culture were significantly associated with progression to leukemia and shorter survival. In multivariate analysis, only CD34 expression (P = .002) and percentage of blasts (P = .05) remained independent significant variables. CD34 was the only significant variable for prediction of survival (P = .05). It is concluded that surface marker analysis at diagnosis and after liquid culture may be a useful tool for the initial evaluation of MDS.
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PMID:Myelodysplastic syndromes: a study of surface markers and in vitro growth patterns. 232 1

The immunophenotype of peripheral blood blast cells was tested in 92 patients with acute myeloid leukemia (AML), who were diagnosed and treated at single centre, St Bartholomew's Hospital, from 1978-1987 with a standard adriamycin, cytosine arabinoside and 6-thioguanine regimen. Immunological analysis involved standard fluorescence flow cytometry and utilized 31 monoclonal antibodies to known myeloid antigens (of CD groups 11b, 11c, 13, 14, 15, 16, w17, 31, w32, 33, 34, 35 and 36), a number of relatively less well studied antibodies with potential specificity for AML, and a series of control antibodies to T and B lymphocytes, platelets, erythrocytes and of widespread distribution (CD45, leucocyte common; HLA-DR). The results highlighted a number of antibodies with wide myeloid reactivity, in addition to CD13 and 33 (present in 66 per cent and 76 per cent of cases, respectively), which may be of immunodiagnostic use. A number of correlations between AML cell immunophenotype and FAB morphology subtype were found; in particular five antibodies (CD11c, 10.1, Tu3, CD15 and CD16), of both predominant granulocytic and monocytic reactivity, reacted with cells of AML-M5 subtype (p less than 0.05). There was no significant correlation between immunophenotype and clinical and pathological features at presentation. Correlation with clinical outcome was not a prominent feature, in contrast to some reports based on multicentre data. However, of particular note was the strong association between early death (at less than 2 months) and the coexpression of Leucocyte Function Associated (LFA) antigens, CD11b and 11c, on patient's blast cells (p = 0.003). The relationship was independent of clinical features and persisted even if AML-M5 cases were excluded. The significance of this latter finding is unclear, but may be related to the known role of CD11b and 11c LFA antigens in the cellular response to infection.
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PMID:Immunophenotype of blast cells in acute myeloid leukemia may be a useful predictive factor for outcome. 240 42

Two monoclonal antibodies, CMRF-7 and 27, which react with cells of the granulocytic series, were obtained from hybridomas cloned from separate fusions. Biochemical studies indicate that both antibodies are of the CD15 group and react with the antigenic determinant 3 alpha-fucosyl-N-acetyl lactosamine (hapten X) expressed on some glycolipids and several different granulocyte glycoproteins with a wide range of molecular weights. The antigen was found on some promyelocytes and more differentiated granulocytes, including neutrophils and some eosinophils, but not basophils. Monocytes, lymphocytes, and erythrocytes were negative for CMRF-7 but neuraminidase treatment revealed "cryptic" sites on monocytes and some lymphoid cells. The antibody CMRF-7 reacted with the majority of acute myeloid leukemia blasts in the FAB categories M2-M5 but less frequently with M1 blasts and was positive with only 5/43 acute lymphoid leukemias. Immunoperoxidase staining of other normal human tissues indicates that this determinant is found on a range of epithelial cells in skin, the gastrointestinal tract and the genitourinary system. In addition some parts of the central nervous tissue and some endocrine organs stained with these antibodies.
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PMID:The tissue distribution of the 3 alpha-fucosyl-N-acetyl lactosamine determinant recognized by the CD15 monoclonal antibodies CMRF-7 and 27. 289 56

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

We have reviewed the clinical, morphologic, immunophenotypic, and cytogenetic features of 52 patients with erythroleukemia (FAB Cooperative Group; AML-M6) studied by the Cancer and Leukemia Group B (CALGB). The purpose of this study was to correlate morphology with the clinical features, immunophenotypes, and karyotypes of neoplastic cells, and with the response to therapy of patients with AML-M6. Thirty-three patients (63%) were male, median age 59 (range 16-81) years, 47 patients (90%) were white, and 42 patients (81%) had a performance status of < 2. Myelodysplastic changes were observed in at least 1 cell lineage in all cases, and in 2 cell lineages in 45 of 52 (86%) cases. Fifty percent or more of cases studied were positive for CD11b, CD13, CD15, CD33, glycophorin-A, and HLA-DR markers. Fourteen of 27 cases (52%) in whom karyotypic analyses were conducted had cytogenetic abnormalities. Five (19%) were simple (< 3 karyotypic abnormalities), while 9 (33%) were complex (> or = 3 abnormalities). We observed either a complete or partial loss of chromosomes 5, 7, or 12p, or the presence of trisomy 8, in 11 of 27 (41%) patients. Cases of AML-M6 were divided into group 1 (14 patients with bone marrow proerythroblasts and basophilic erythroblasts > 25% of all erythroblasts) and group 2 (38 patients with proerythroblasts and basophilic erythroblasts < or = 25% of all erythroblasts). We observed no significant differences between groups 1 and 2 in regard to sex, age, race, performance status, percentage of blood erythroblasts or myeloblasts, percentage of bone marrow erythroblasts, and periodic acid-Schiff (PAS) or myelodysplasia scores. Six of 6 (100%) patients of group 1, and 7 of 21 (33%) patients of group 2, had normal karyotypes (P = .006). Nine of 13 (69%) patients of group 1 and 15 of 33 (45%) patients of group 2 had a complete remission (CR) (P = .2). Eight of 11 (73%) cytogenetically normal patients achieved CR: 5 of 6 (83%) in group 1, and 3 of 5 (60%) in group 2. Five of 12 (42%) cytogenetically abnormal patients achieved CR. No difference in duration of survival (group 1, median = 4.6 months vs. group 2, median = 10.2 months; P = .93) was observed between the 2 groups. We conclude that AML-M6 is typified by multilineage involvement of hematopoietic cells. The morphology of erythroblasts in patients with AML-M6 may correlate with cytogenetic abnormalities and rate of CR.
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PMID:Morphologic characteristics of erythroleukemia (acute myeloid leukemia; FAB-M6): a CALGB study. 774 Nov 35

The clinicopathological features and the prognostic significance of acute myeloid leukaemia (AML) with trisomy 11 are currently unknown. In this study we describe 15 adult AML cases with trisomy 11. Trisomy 11 was the sole chromosomal anomaly in eight cases; the remaining seven cases were characterized by +11 in association with other karyotypic aberrations. Patients ages ranged from 34 to 79 years. 12 patients were male; three were female. Although there was no correlation of trisomy 11 with any specific FAB subgroup [M2 (n = 7), M1 (n = 5), M4/5 (n = 2), M3 (n = 1)] less mature forms predominated. Immunologically, the leukaemic blasts showed a strikingly consistent stem cell phenotype with expression of HLA-DR, CD34 and the myeloid antigens (CD15, CD33 and/or CD13). In addition, two cases expressed the B-cell associated antigen CD19. The presence of trilineage dysplasia, suggesting the presence of an underlying myelodysplasia (MDS), was observed at presentation in five cases; in another case MDS was evident at relapse only. Unexpectedly, MLL gene rearrangements were observed in two of four cases characterized by trisomy 11 as the sole karyotypic abnormality; however, MLL aberrations were not identified in three cases with trisomy 11 accompanied by other karyotypic anomalies. The majority of patients in each subgroup (i.e. those with and without additional cytogenetic abnormalities) achieved a short first complete remission (CR) (mean 8 months) and failed to obtain a second CR. Only one patient in each trisomy 11 subgroup is in a continuous CR for > 34 months. These findings suggest that trisomy 11 leukaemia is characterized by a stem/progenitor cell immunophenotype with poor response to standard chemotherapeutic regimens and an unfavourable prognosis.
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PMID:Trisomy 11: an association with stem/progenitor cell immunophenotype. 779 46

The membrane phenotype of AML clonogenic cells (L-CFU) was analyzed in 19 AML patients using an in vitro culture technique after a complement-mediated lysis assay employing a panel of six monoclonal antibodies (McAb) -HLA-DR, FMC56 (CD9), FMC27 (CD9), CD14, CD15, CD41a-. Our results show that L-CFU has a heterogeneous but immature phenotype lacking on the expression of differentiation antigens (CD14, CD15, CD41a). In addition, we observed that the L-CFU phenotype is different from that of the whole blast cell population. Interestingly, L-CFU showed a higher expression of HLA-DR antigens with respect to their progeny. Upon analyzing whether the L-CFU phenotype was related to both the morphological and immunological features of AML blast cells, it was observed that, while there is no correlation with the FAB classification, there was a partial relationship between the immunological phenotype of AML blast cells and that of L-CFU. Accordingly, the more immature AML cases showed a more differentiated L-CFU phenotype (HLA-DR+, CD9+, FMC27+) when compared with cases with a more mature blast cell phenotype. These results suggest that those AML cases with a relatively immature myeloblastic phenotype may arise from a progenitor cell that has undergone partial differentiation and that is unable to acquire myeloid differentiation antigens, while those AML cases with mature blast cells might emerge from a very early L-CFU that has the capacity to undergo a greater degree of differentiation.
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PMID:The phenotype of L-CFU and its correlation with the immunological characteristics of the blast cell population in AML. 801 63

Acute promyelocytic leukemia represents 5-10% of acute myeloid leukemia cases (AML) recorded in the literature, occurring more frequently in young adults. It has a special clinical and biological behaviour when compared to the other forms of AML, being characterized by a particular morphology of blast cells (M3 in FAB classification), translocation of chromosomes 15;17, and disseminated intravascular coagulation at diagnosis or after the onset of chemotherapy. Within this AML subgroup there are 2 morphological subsets called the hypergranular promyelocytic leukemia and the hypogranular or variant form. We have studied clinical and laboratory aspects of 19 cases of AML M3 out of 217 AML cases, and observed a high incidence of failure to recognize the M3 variant form, although its diagnosis has been mainly based on cytomorphology. Only 4 out of 8 cases of the variant form received in our laboratory were correctly diagnosed, being the other 4 cases wrongly identified as the myelomonocytic subset of AML (M4). Immunophenotyping with monoclonal antibodies using CD2 and CD7 as T cell markers, CD10 and CD19 as B cell markers and CD33, CD13, CD14, CD15 and anti MPO as myeloid markers is a complementary diagnostic tool that permits solving difficult cases. It is important to classify AML correctly because of the special therapeutic and prognostic features of AML M3, which differently from other AML forms, has been successfully treated with cellular differentiating agents.
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PMID:[M3 variant leukemia: clinical and diagnostic features]. 816 87


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