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)

The newly produced monoclonal antibody (mAb) LF61 detects a molecule restricted to hairy cell leukaemia (HCL) among B-cell non-Hodgkin's lymphomas. In particular, the percentage of LF61 + HCL cells in different cases ranges from 10% to 100%. In normal lympho-haemopoietic tissues LF61 reacts with only about 2% of T-cells, mostly of the CD8 subset in the peripheral blood, extrafollicular areas of the tonsil, red pulp of the spleen and thymic medulla. Expression of the LF61 molecule is observed following stimulation of peripheral blood lymphocytes with phytohaemagglutinin (PHA) or pokeweed mitogen (PWM), suggesting that it represents an activation antigen. Due to its restricted reactivity with a small subset of normal CD8 + T-cells, LF61 in combination with a CD22 mAb is highly suitable for monitoring residual disease in interferon or deoxycoformicin-treated HCL patients. Polyacrylamide gel gradient electrophoresis shows that LF61 precipitates a 150 kDa, 125 kDa, 105 kDa trimeric molecule from the surface of HCL cells. Immunohistological and immunobiochemical results show that this molecule is the same as the one recognized by the still unclustered anti-HCL mAb B-ly7.
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PMID:LF61: a new monoclonal antibody directed against a trimeric molecule (150 kDa, 125 kDa, 105 kDa) associated with hairy cell leukaemia. 226 7

We have analysed the immunological characteristics of blasts from 89 acute lymphoblastic leukaemia (ALL) cases (62 adults and 27 children), by using a panel of antilymphoid and myeloid associated monoclonal antibodies (McAb) and the APAAP method, which detects membrane and cytoplasmic expression of antigens. The McAb CD19 was the marker most consistently expressed in B lineage ALL, being positive in 100% of cases, compared to CD24 and CD22 expressed in 82% and 79%, respectively. Similarly, for the T lymphoid lineage, the McAb CD3 was the most reliable and specific marker, being expressed in all T-ALL cases including those with an early thymic phenotype (CD7+, TdT+). Lymphoblasts from eight adults (12.9%) and three children (11.1%) expressed one to four myeloid associated antigens recognized by CD13, CD14, CD33 and anti-myeloperoxidase. There were no substantial clinical and morphological differences between the two ALL groups with or without myeloid associated markers. However, the presence of myeloid associated markers in adult ALL was associated with a significantly lower complete remission (CR) rate (P = 0.05) and with a shorter survival (P = 0.001); this variable was independent of advanced age and high WBC. It is concluded that immunophenotypic analysis in ALL should include myeloid markers for its probable prognostic implications.
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PMID:Clinical significance of the presence of myeloid associated antigens in acute lymphoblastic leukaemia. 237 6

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.
Leukemia 1990 Sep
PMID:Phenotypic, genotypic, cytochemical, and ultrastructural characterization of acute undifferentiated leukemia. 239 82

Terminal deoxynucleotidyl transferase (TdT) is a useful marker for normal lymphocyte precursors and acute lymphoblastic leukemia (ALL). Our previous studies, however, have shown that for monitoring minimal residual disease in the circulation, assay for TdT alone is not sufficiently specific to distinguish leukemia cells from the background of rare normal blood TdT+ cells. In an attempt to increase specificity for leukemic cells, we have used double and triple immunophenotypic analysis to characterize normal circulating and bone marrow TdT+ cells. Overall, normal TdT+ cells were about 1000-fold more frequent in the marrow than in the blood. More than 75% of TdT+ cells in both the blood and marrow expressed the CD34, CD22, and HLA-DR antigens. However, circulating TdT+ cells infrequently expressed CD19 (4.5%) and CD9 (2.3%), compared with their marrow counterparts (74% and 47%, respectively). The brightly staining CD10+ phenotype, frequently associated with ALL blasts, was significantly less common among normal blood (5.7%) than marrow (31%) TdT+ cells. Although T-lineage markers were rarely expressed on TdT+ cells in either site, CD7+ cells were far more prevalent within the circulating TdT+ subset (4%) than among the marrow population (less than 0.2%). The results suggest a selective release of lineage-uncommitted and/or thymus-destined TdT+ cells from the marrow into the circulation. Moreover, since CD19, CD9, and high-density CD10 are frequently found on ALL blasts, staining for these markers on TdT+ cells in the circulation should improve the specificity of assay for residual common ALL cells. Likewise, assay for CD5+ and possibly CD7+ TdT+ cells in either marrow or blood should provide a very sensitive method of detection of T-ALL blasts.
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PMID:Phenotypic heterogeneity of TDT+ cells in the blood and bone marrow: implications for surveillance of residual leukemia. 233 29

A case of chronic lymphocytic leukemia (CLL) treated with chlorambucil, followed by the development of an acute monoblastic leukemia, is described. Cytofluorometric quantitative immunophenotype was determined during the blastic phase. Whereas small lymphocytes displayed a CD19+; CD24+; CD37+; CD5+ phenotype, the blastic population exhibited, besides CD13, CD14 and CD15 positivity, which is usually noted in such a monoblastic leukemia, definite CD9, CD10, CD22, CD24, CD37, CD5 and CD4 staining. Such results argue against a complete independence between the two clones, although their similarity could not be demonstrated.
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PMID:Acute monocytic leukemia with B cell markers expression following B chronic lymphocytic leukemia. 258 3

The expression of two myeloid antigens identified by the monoclonal antibodies (McAb) MCS2 (CD13) and MY9 (CD33) was investigated in 136 cases of leukaemia. MCS2 was positive in blast cells of 78 of 88 (88.5%) and MY9 in 51 of 81 (64%) cases of acute myeloid leukaemia (AML) and chronic granulocytic leukaemia in myeloid blast crisis. One or other McAb, or both, were positive in all but 2 (2.3%) of these cases. MCS2 was more sensitive than MY9 to detect blasts of the myeloid lineage due to its most frequent reactivity in the cytoplasm of fixed cells by the immunoperoxidase (IP) technique compared with its membrane expression on cell suspensions by immunofluorescence (IF). MY9 was not suitable for tests on fixed cells. MCS2 was positive by IP but not by IF in 24% of AML, but the reverse was not observed. This suggests that the antigen detected by MCS2 is expressed in myeloblasts first in the cytoplasm and later on the cell membrane, pattern which is similar to that of the early antigens CD3 and CD22 in T and B lineage lymphoblasts, respectively. MCS2 was always positive in FAB types of AML-involving myeloblasts (M1-M4), including cases of undifferentiated morphology (M0), whilst MY9 was more frequently positive in monocytic leukaemia (M5). On the other hand, MCS2 was positive in 4 of 33 cases of acute lymphoblastic leukaemia and MY9 in 1. We conclude that both McAb, particularly MCS2, contribute to the better characterisation of myeloid leukaemias but that other tests are required to clarify the nature of the blasts when unexpected reactivities are observed.
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PMID:Early expression of MCS2 (CD13) in the cytoplasm of blast cells from acute myeloid leukaemia. 290 4

Cells from two patients with primary mediastinal tumors of clear cell type were characterized by immunological and molecular biological techniques. In both cases a B cell immunophenotype was suggested by the positive staining for the B1 (CD20), B4 (CD19), Leu 14 (CD22), as well as staining with other B monoclonal antibodies by immunohistochemistry. However, no definitive evidence for the expression of Ig light or heavy chains at the protein level was found. Southern blot analysis of Ig heavy and light chain gene rearrangements revealed clonal B cell populations in both cases. There was no indication of a somatic joining of T cell receptor (TCR) genes using probes for TCR beta and or TCR gamma genes. Thus, our results suggest a clonal B cell origin of clear cell lymphomas in the mediastinum.
Leukemia 1989 Feb
PMID:Clonal immunoglobulin gene rearrangements in primary mediastinal clear cell lymphomas. 291 Dec 6

The expression of antigens detected by monoclonal antibodies of the CD22 and CD3 groups was studied, by immunofluorescence (IF) on cell suspension and by immunoperoxidase (IP) on cells fixed on cytospin slides, in a range of B- and T-cell malignancies. CD22 was demonstrated in the B-cell leukemias more frequently by IP than by IF; in B-lineage acute lymphoblastic leukemia (ALL) it was positive only by IP. In chronic lymphocytic leukemia and lymphoplasmacytic tumors approximately 40% of cases were CD22 positive by IP but few by IF. In other disorders of mature B cells, CD22 was positive by both methods in most cases. CD3 was demonstrated by IP in all 48 cases of T-cell leukemia and lymphoma regardless of the maturation stage (i.e., from early thymic to mature T cells). This was not the case by IF, where only 16% of T-ALL and 73% of cases with postthymic T-cell leukemias were recorded as positive. The greater reactivity of CD3 and CD22 by IP reflect the early cytoplasmic expression of the antigens in immature T and B cells, respectively, as well as the possible greater sensitivity of the IP method. These differences should be taken into account when describing results in lymphoid malignancies. CD3 was not expressed in cells from any of the B-cell leukemias, and likewise, CD22 was not demonstrated in any of the T-cell disorders, confirming that both reagents are highly specific for their respective lineages.
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PMID:Different expression of CD3 and CD22 in leukemic cells according to whether tested in suspension or fixed on slides. 297 27

Ricin A chain-containing immunotoxins (IT-As) specific for the human B-cell antigen, CD22, were prepared from 4 monoclonal antibodies (MAbs) or their Fab' fragments: RFB4, HD6, UV22-I and UV22-2. The ITs were tested for their ability to kill cells from the Burkitt lymphoma line, Daudi, the pre-B-cell leukemia line, NALM-6, and the myeloma cell line, ARH-77. Daudi expresses high levels of CD22, whereas NALM-6 and ARH-77 express low levels of CD22. The IgG-RFB4-A was highly toxic to all 3 cell lines; it killed 50% of the Daudi cells at a concentration of 1.2 x 10(-12) M and 50% of NALM-6 and ARH-77 cells at concentrations of 1.5 to 2.1 x 10(-11) M. IgG-RFB4-A was 10-30 times more toxic to Daudi cells than were the IgG-As constructed from the other 3 CD22 MAbs and 10 times more toxic than ricin itself. IT-As constructed from the Fab' fragments of the 4 CD22 antibodies were 2 to 5 times less toxic to Daudi cells than their IgG-A counterparts. Fab'-RFB4-A was twice as toxic to Daudi cells as ricin, whereas the other Fab'-As were about 7 times less toxic than ricin. Scatchard analyses of the binding of the radio-iodinated antibodies to Daudi cells showed that the intact RFB4 antibody bound 3-10 times more strongly than the other antibodies, whereas the Fab'-RFB4 bound 1.2 to 3.5 times more strongly than the Fab' fragments prepared from the other antibodies. Thus, the potent cytotoxic activity of the RFB4-As appears to derive, in part, from their superior binding affinity. Prior studies have shown that UV22-I and HD6 cross-react with certain normal human tissues lacking cells of B-cell lineage, whereas UV22-2 and RFB4 are B-cell-specific. This fact, together with its superior potency as an IT-A, suggests that RFB4 is the antibody of choice for preparing Fab'-As or IgG-As for in vivo therapy of human B-cell leukemias and lymphomas.
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PMID:Evaluation of four CD22 antibodies as ricin A chain-containing immunotoxins for the in vivo therapy of human B-cell leukemias and lymphomas. 326 28

The distribution of the gp40-45 Kd antigen bound by the WR17 monoclonal antibody of IgG2 subclass in normal lymphoid tissue was characterized by immunohistochemistry and immunofluorescence staining with flow cytometric analysis. The predominant staining pattern observed was characteristic of an anti-pan-B-lymphocyte reagent. Weak reactions were observed by immunofluorescence staining of viable cell suspensions with all neutrophils and T-lymphocytes in some normal donors. In tissue sections, B-lymphocytes were stained and no cross reactions were observed with T-lymphocytes, although macrophages stained in some sections. A range of T- and B-cell malignancies were stained with WR17 and the reactivity compared to that observed with other monoclonal antibodies in the CD19, CD21 and CD22 clusters. All B-non-Hodgkin's lymphomas, B-chronic lymphocytic, prolymphocytic and hairy cell leukaemia cells examined were stained by WR17 in indirect immunofluorescence assays, whilst the T-cell tumours were negative. The same pattern was observed in cryostat sections of malignant tissue and in addition some tissue macrophages expressed the CD37 antigen cytoplasmically. Intra-tumour heterogeneity of staining was observed with all the monoclonal antibodies tested, although overall WR17 consistently stained B-cell tumours even when expression of the CD19 pan-B-lymphocyte antigen could not be detected with some monoclonals. Monoclonal antibodies, such as WR17, within the CD37 cluster and binding to the gp 40-45 Kd molecule, bind to mature B-lymphocytes and identify the majority of B-cell malignancies.
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PMID:Use of the monoclonal antibody WR17, identifying the CD37 gp40-45 Kd antigen complex, in the diagnosis of B-lymphoid malignancy. 330 45


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