Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biphenotypic acute leukemias account for 4% to 8% of all acute leukemias. Most of these leukemias are of myeloid-B-cell or myeloid-T-cell lineage. Acute myeloid-natural killer cell leukemia has been recognized recently. We report the first case, to our knowledge, of CD56(+) acute leukemia showing unequivocal myeloid and B-cell differentiation in a 20-year-old woman, whose blast cells were positive for myeloperoxidase, CD13, CD33, CD117, terminal deoxynucleotidyl transferase, CD19, CD20, CD22, CD34, HLA-DR, and CD56 but negative for CD3, CD5, CD7, and CD10. Rare Auer rods were identified in the blast cells. Polymerase chain reaction assays showed rearrangement of immunoglobulin heavy-chain gene and absence of Epstein-Barr virus DNA. We propose that this novel form of multilineage leukemia may represent the neoplastic counterpart of a progenitor that can give rise to myeloid, B, and natural killer cells.
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PMID:Acute leukemia with myeloid, B-, and natural killer cell differentiation. 1256 62

Panels of immunological markers are useful in refining diagnosis in view of certain variability between B-cell leukaemias. A statistical multivariate approach was used on 100 B leukaemias (preliminary sample) to explore the potential value of the combination of CD43, and the classical markers CD5, CD23, CD79b, FMC7, CD22 and surface immunoglobulin to differentiate chronic lymphoid leukaemia (CLL) from lymphoma (non-CLL). CD43 was highly effective (P < 0.00001) and its inclusion in the panels improved the accuracy of discrimination in a 'control' sample of 74 B leukaemias to 98.6%. Inclusion of CD43 facilitates the diagnosis of B-lymphoproliferative disorders and improves their classification.
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PMID:Cell surface CD43 determination improves diagnostic precision in late B-cell diseases. 1258 Sep 68

The anti-CD19 (HD37-dgRTA) and anti-CD22 (RFB4-dgRTA) immunotoxins (ITs) are murine IgG(1) monoclonal antibodies (Mabs) conjugated to a deglycosylated ricin A chain (dgRTA). They are effective in killing B-lineage non-Hodgkin's lymphoma (NHL) cells in vitro, in vivo and in adult patients with B-lineage NHL. The potential of these agents for the treatment of childhood B-precursor acute lymphoblastic leukemia (ALL) is unknown. The anti-CD19 and anti-CD22 ITs should have anti-tumor activity against childhood B-lineage ALL since both target antigens are expressed on the surface of these cells. We have previously shown that, in vitro these two ITs selectively kill leukemia cells obtained from children with leukemia. To evaluate the efficacy of our ITs in an in vivo model we injected the human pre-B ALL cell line, NALM-6-UM1, into severe combined immunodeficient (SCID) mice. We tested the ability of two ITs to prolong survival or cure mice of both early and advanced tumors. In early disease, treatment with HD37-dgRTA, RFB4-dgRTA, or Combotox (an equimolar concentration of the two ITs) significantly improved their survival. In advanced disease, treatment with RFB4-dgRTA or Combotox significantly improved survival. Overall there were 10 long-term survivors who were cured, as determined by survival beyond 150 days with no evidence of disease as determined by polymerase chain reaction (PCR) analysis.
Leukemia 2003 Feb
PMID:Treatment of SCID/human B cell precursor ALL with anti-CD19 and anti-CD22 immunotoxins. 1259 32

CD20 is a B-cell differentiation antigen and known to induce apoptosis in Burkitt's lymphoma/leukemia (BL) cells upon antibody-mediated crosslinking. We examined the biological effect of CD20 crosslinking on BL cell lines and observed that apoptosis induction is accompanied by activation of multiple caspases, including caspase-8, -9, -3, -2, and -7. Further investigation revealed a clear synergism between apoptosis mediated by CD20 and by B-cell antigen receptor (BCR). Examination of the effect of simultaneous crosslinking of other cell surface molecules with crosslinking of CD20 or BCR on apoptosis induction showed that these molecules had either a synergistic or inhibitory effect on induction of apoptosis. It is worth noting that some molecules had a different effect on CD20- and BCR-mediated apoptosis. Simultaneous crosslinking of the molecules CD10, CD22, CD72, and CD80 inhibited BCR-mediated apoptosis, but enhanced CD20-mediated apoptosis. Further studies revealed that regulation of CD20-induced apoptosis by other costimulatory molecules is achieved by modification of caspase activation. CD20-mediated apoptosis in BL cells may provide not only a model for understanding the mechanism regulating clonal selection of B cells but a new therapeutic strategy for BL patients.
Leukemia 2003 Jun
PMID:Costimulatory signals distinctively affect CD20- and B-cell-antigen-receptor-mediated apoptosis in Burkitt's lymphoma/leukemia cells. 1276 85

The role of flow cytometry (FC) in the diagnosis of lymphoid lesions by fine-needle aspiration (FNA) is well established. However, studies evaluating the usefulness of FC in serous cavity effusions (SCE) are few. We performed a retrospective review of 115 consecutive SCE with concurrent FC analysis, comparing the provisional cytopathologic diagnosis (PCD), i.e., before the FC results were added, with final diagnoses as modified by subsequent FC immunophenotyping. The predominant clinical indication for the FC analysis was the presence of a spontaneous SCE in a patient with a history of malignant lymphoma. Three- or four-color analysis was performed using antibodies against CD45, CD71, CD33, CD22, CD19, CD20, kappa, lambda, CD5, CD3, and CD56. The PCD was benign in 47%, atypical in 16%, and malignant in 37% of cases. The latter category consisted mostly of malignant lymphoma (n = 32), but also included acute lymphoblastic leukemia (1 case), T-cell lymphoma/leukemia (2 cases), acute myelogenous leukemia (1 case), multiple myeloma (1 case), Hodgkin's lymphoma (1 case), sarcoma (1 case), and adenocarcinoma (4 cases). In 18 cases (16%), the PCD was later modified by the FC results from atypical/suspicious to benign (8) and from benign or atypical/suspicious to malignant (10 cases). The latter group included acute natural killer (NK) cell leukemia (1 case), chronic lymphocytic leukemia (1 case), mantle cell lymphoma (2 cases), follicular lymphoma (3 cases), angioimmunoblastic lymphoma (1 case), large cell lymphoma (1 case), and multiple myeloma (1 case). As expected, FC was noncontributory in cases of Hodgkin's lymphoma and nonlymphoid malignancies. In summary, immunophenotyping by FC modified the PCD significantly in 16% of SCE, permitting appropriate cancer staging and management. The above data underscore the importance of FC as an adjunct to cytomorphology in SCE.
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PMID:Flow cytometry as an adjunct to cytomorphologic analysis of serous effusions. 1288 43

A novel B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) cell line, NALM-35, was established from the peripheral blood of a 40-year-old woman at diagnosis of ALL. Imunophenotyping showed BCP type III characteristics including expression of TdT, CD10, CD19, CD22, CD79a and HLA class II. T-cell and myeloid-associated antigens tested were negative except CD5 and CD28. The surrogate light chains CD179a and CD179b were positive. NALM-35 cells have the morphological appearance of lymphoblasts. Cytogenetic analysis of NALM-35 revealed an abnormal karyotype with 46, XX, add(9)(p11). Southern blot analysis of the immunoglobulin genes status of NALM-35 at 10 months after establishment showed germ line configuration of the kappa and lambda light chain genes, and rearrangement of the mu heavy chain gene. DNA fingerprinting, chromosomal analysis and immunophenotyping proved that NALM-35 was clonally derived from the primary leukemia cells. The established cell line may provide a useful model system and unprecedented opportunities for analyzing the multitude of biological aspects of normal and neoplastic B-lymphocytes and their precursors.
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PMID:Establishment and characterization of new B-cell precursor leukemia cell line NALM-35. 1288 57

Multiparameter flow cytometry can allow for accurate lineage assignment of leukaemia cell populations in approximately 99% of cases, whereby the emphasis lies in the word 'can'. Despite the fact that the very few markers that are lineage-specific are localized inside the cell (e.g. myeloperoxidase, lactoferrin, cytoplasmic CD3, cytoplasmic CD22), several investigators still shy away from including these essential test elements in their routine panels. Of course, the staining of intracellular antigens requires the added effort of determining optimal conditions. Published suggestions often need to be revised, and cell lines must be used as positive and negative controls. The same holds true for other new and exciting applications of flow cytometry, such as the monitoring of minimal residual disease (MRD) or the establishment of physiological assays (e.g. measuring the activity of drug-efflux pumps). The beauty of-and unfortunately for some, the problem with-multiparameter flow cytometry is that although immunophenotyping by flow cytometry has become a routine approach to the diagnosis of haematological malignancies it is a discipline that is still in development. New antibodies are continually being introduced and new diagnostic and prognostically relevant subtypes are being published in almost every issue of the major scientific journals. It is therefore very important for the flow cytometrist not only to strive for optimal performance of all tests employed but also to keep up with new knowledge and to incorporate it into the interpretation of routine specimens. We owe it to our patients to diagnose their disease accurately and in accordance with accepted standards of interpretation so that the treating physicians can trust immunophenotyping results and act accordingly in the management of their patients.
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PMID:How to optimize multiparameter flow cytometry for leukaemia/lymphoma diagnosis. 1459 50

Like CD19 or CD56, CD22 in non-lymphoid leukemia has been considered an aberrantly expressed antigen. CD22 had been believed to be restricted to B lymphoid, however, it was also found to be expressed in human basophils. Mature basophils are unique granulocytes expressing CD13, CD22 and CD25. To estimate whether the expression of CD22 in non-lymphoid leukemia is aberrant or related to basophilic character, we analyzed 108 patients with primary and secondary leukemia. Among non-lymphoid leukemias, surface CD22 expression was more frequently observed in peroxidase-negative AML and secondary leukemia, and was usually observed simultaneously with CD13 and CD25. Samples obtained from 17 cases were further analyzed, and all the Fc epsilon R1-positive cases were observed in peroxidase-negative AML and secondary non-lymphoid leukemia, and mostly expressed CD13, CD22 and CD25. Therefore, surface CD22 expression in non-lymphoid leukemia was thought to relate to basophilic phenotype in some cases. Like CD22, some of the so-called aberrantly expressed antigens may not actually be aberrant, but are expressed in a stage of differentiation and maturation of progenitors. Moreover, CD22 may be one of target molecules for treatment of CD22-positive, poorly prognostic leukemia.
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PMID:Simultaneous expression of CD13, CD22 and CD25 is related to the expression of Fc epsilon R1 in non-lymphoid leukemia. 1515 90

The main topic of this article is B cell development and differentiation, with a special focus on the mechanisms and molecules that regulate the expression of humoral immunity. Molecular epidemiological analysis was performed on the genes responsible for the X-linked agammaglobulinemia (XLA) phenotype of the majority of Italian patients and their distinct mutations were characterized. Mutations in Bruton's tyrosine kinase (BTK), a member of Tec Family of protein tyrosine kinases, have been found to be mainly responsible for XLA disease. The exact function of BTK in signal transduction is not yet known; thus, the specific role of BTK in receptor-dependent calcium signaling and the pro-antiapoptotic regulatory activity was addressed by transfecting RAMOS-1, a BTK-deficient human Burkitt's/B cell leukemia line with wild-type and mutant constructs. This work may provide clues about critical sites in the molecule and give support for gene therapy as a potential successful approach to XLA. Another aspect of this research is the identification and dissection of the molecular events that are likely to be directly related to the ability to express various isotypes of immunoglobulin with differing function and certain B cell immunodeficiency, mainly common variable disease and non-X-linked hyperIgM. B cell development and maturation steps in different compartments of the immune system are tracked by the analysis of cell-surface molecules and components of the signal transduction pathways, i.e. CD40, CD30, CD27, CD38, CD22 and CD24. A few components involved in B cell development, maturation and differentiation and their specific functional role are at least partially known, but these are far from fitting into an understandable pathway at present.
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PMID:Insight into B cell development and differentiation. 1517 20

Translocation (14;14)(q11;q32) or inv(14)(q11q32) is a common cytogenetic aberration in T-cell leukemia associated with ataxia-telangiectasia (AT); however, rare reports have indicated that this abnormality also occurs in B-lineage acute lymphoblastic leukemia (ALL). We report here two cases with common-type ALL exhibiting the chromosomal aberration t(14;14)(q11;q32). The immunophenotype showed the blasts were positive for CD9, CD10, CD38, CD22, and CD15 in case 1 and positive for CD2, CD9, CD10, CD19, CD38, CD20, and CD22 in case 2, but negative for CD3, CD4, and CD8 expression in both cases. The cytogenetic analysis revealed del(6)(q22), and t(14;14)(q11;q32) in case 1 and t(14;14)(q11;q32),+mar in case 2. Fluorescence in situ hybridization (FISH) and sequential R-banding FISH assay with dual-color break-apart IGH probe confirmed that t(14;14)(q11;q32) involved the IGH gene in our cases. The results indicate that the t(14;14)(q11;q32) involving IGH at 14q32 in B-lineage ALL in our cases differ from those reported to involve the TCL1 gene on 14q32.1 in T-cell leukemia associated with AT. Sequential R-banding and FISH provide precise analysis of alterations of chromosomes and genes involved.
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PMID:IGH gene involvement in two cases of acute lymphoblastic leukemia with t(14;14)(q11;q32) identified by sequential R-banding and fluorescence in situ hybridization. 1526 34


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