Biomedical subjects

F R Davey

Publications and source records attributed to F R Davey.

At least 37 records · Page 2Linked to original sources

PubMed1994

Detection of MLL gene rearrangements in adult acute lymphoblastic leukemia. A Cancer and Leukemia Group B study.

Specific structural rearrangements involving chromosome band 11q23 occur in a variety of hematologic malignancies, including an estimated 2-7% of patients with acute lymphoblastic leukemia (ALL). Translocations involving chromosome band 11q23 have been associated with a poor prognosis in patients with ALL. Recently, a gene known as MLL has been identified which is involved in acute lymphoid and myeloid leukemias with rearrangements at 11q23. A 0.74-kilobase (kb) cDNA probe from the MLL gene can detect both common and uncommon rearrangements involving MLL on conventional Southern blots. We studied 86 newly diagnosed adults entered on an ALL clinical trial to investigate the incidence of MLL gene rearrangements and to determine clinical, morphologic, immunologic and cytogenetic characteristics of such patients. Two of 86 patients had MLL gene rearrangements detected by Southern blot analysis. One of these 86 patients had an 11q23 translocation by cytogenetic analysis whereas the second patient was unevaluable by standard cytogenetic analysis. Southern blot identification of rearrangements involving MLL, especially in patients with limited material for cytogenetic analysis, can provide critical diagnostic and prognostic information which may be useful in the clinical management of patients with these abnormalities.

Adolescent↗

PubMed1993

Cigarette smoking and risk of acute leukemia: associations with morphology and cytogenetic abnormalities in bone marrow.

BACKGROUND: Cigarette smoking may be a risk factor for leukemia. No detailed biological mechanism has been proposed, but a causal link is made plausible by evidence of systemic effects of cigarette smoke and the presence in cigarette smoke of chemicals that have been associated with leukemia risk. PURPOSE: Our purpose was to investigate the leukemia risk associated with cigarette smoking in a multicenter case-control study of acute leukemias in adults. METHODS: Adults aged 18-79 with newly diagnosed leukemia were contacted to participate in this epidemiologic study when they entered a clinical trial to be treated under protocols sponsored by Cancer and Leukemia Group B. Smoking histories for 610 patients with acute leukemia and 618 population control subjects were obtained by telephone interviews. We examined bone marrow samples and classified patients by morphology of leukocyte precursor cells according to the French-American-British (FAB) classification system and, for 378 patients, by the presence or absence of specific clonal chromosome abnormalities. We calculated odds ratios (ORs) for risk of leukemia associated with smoking cigarettes. ORs were adjusted for age, race, and sex. RESULTS: Smoking was associated with only a modest increase in risk for leukemia overall (adjusted OR = 1.13; 95% confidence interval [CI] = 0.89-1.44). However, among participants aged 60 and older, smoking was associated with a twofold increase in risk for acute myeloid leukemia (AML) (OR = 1.96; 95% CI = 1.17-3.28) and a threefold increase in risk for acute lymphocytic leukemia (ALL) (OR = 3.40; 95% CI = 0.97-11.9). Among older persons, risks increased with amount and duration of smoking. Smoking was associated with increased risk for AML classified as FAB type M2 at all ages, with ORs of 1.70 (95% CI = 1.00-2.90) for those younger than 60 and 3.50 (95% CI = 1.53-8.03) for those aged 60 and older. Smoking was also associated with ALL type L2 at all ages, with ORs of 1.72 (95% CI = 0.90-3.27) for those younger than 60 and 5.34 (95% CI = 1.03-27.6) for those who were older. Smoking was more common among patients with specific chromosome abnormalities in AML [-7 or 7q-, -Y, +13] and in ALL [t(9;22)(q34;q11)]. CONCLUSIONS: Cigarette smoking is associated with increased risk for leukemia and may lead to leukemias of specific morphologic and chromosomal types. The association varies with age. IMPLICATION: Examining discrete subtypes of disease may permit more accurate assessment of risk. As standardized morphologic classification and cytogenetic and molecular evaluation of leukemia patients becomes more common, epidemiologic studies that take advantage of these advances will begin to contribute to the identification of additional risk factors and mechanisms in acute leukemia.

Acute Disease↗

PubMed1993

Phenotypic markers and BCL-1 gene rearrangements in B-cell chronic lymphocytic leukemia: a Cancer and Leukemia Group B study.

The markers, CD11b, CD11c, CD14, CD21, CD23, CD25, CD38, and FMC7 were correlated with morphologic and other laboratory and clinical characteristics of 127 patients with untreated CD5+ chronic lymphocytic leukemia (CLL). Only CD38 and CD21 were significantly associated with atypical CLL morphology. The integrin associated markers CD11b and CD11c were associated with lower leukocyte count (white blood cell count [WBC]) and lower Rai stage. By contrast, the activation antigen CD23 was associated with a higher WBC, higher Rai stage, younger age group, and the presence of lymphadenopathy. Therefore, we conclude that CD23 positivity may reflect a more aggressive form of CLL, and CD11b and CD11c positivity a less aggressive form. The BCL-1 gene rearrangement was present in 5 of 84 (6%) CLL cases examined and was associated with atypical morphology and surface expression of CD11b. Patients with a BCL-1 gene rearrangement may represent a CLL subset or possibly a different B-cell disease.

Adult↗

PubMed1992

Morphologic characteristics of acute lymphoblastic leukemia (ALL) with abnormalities of chromosome 8, band q24.

The CALGB prospectively studied 140 adult acute lymphoblastic leukemia (ALL) patients for cytogenetic abnormalities. Seven (5%) patients with adequate cytogenetic preparations had t(8;14)(q24;q32) or t(8;22)(q24;q11). Patients were compared with non-8q24 patients for clinical and laboratory characteristics, response to therapy, and survival. The median age of patients with translocations involving 8q24 (71% males) was 40 years. Forty-three percent had lymphadenopathy, 29% splenomegaly, and 29% hepatomegaly. None exhibited central nervous system (CNS), skin, or gum involvement. These features did not differ significantly from non-8q24 ALLs. Patients with 8q24 translocations had higher hemoglobins (11.5 vs. 9.8 g/dl; P = 0.04) and lower percentage of blasts in the peripheral blood (8.5% vs. 69%; P = 0.007). Although all seven were finally categorized as ALL-L3, a marked variation in the proportion of typical L3 blasts was observed that initially resulted in the diagnoses of ALL-L2 in three cases and prolymphocytic leukemia in one. In five of five patients, the blasts typed as B cells (SIg+ and CD19+). Complete remission rates for patients with 8q24 translocations were 43%, whereas they were 68% for non-8q24 ALLS (P = 0.22). Furthermore, patients with 8q24 abnormalities exhibited significantly shorter survival (4.8 vs. 18.4 mo; P less than 0.001). We conclude that ALL with translocations of 8q24 in adults shows a mature B-cell immunophenotype (SIg+), poor prognosis and morphology ranging from classical ALL-L3 to ALL with a subpopulation of L3 cells. Thus, the diagnosis of ALL-L3 should be made when blastic cells possess a mature B-cell immunophenotype (SIg+) and an 8q24 translocation, even though the number of L3 cells is low.

Adult↗

PubMed1992

The use of monoclonal antibodies against primary myeloid granules in normal and leukemic cells.

Three monoclonal antibodies, K101, D46, and H36/71 (CD15), reactive with membrane components of primary granules of human promyelocytes, were studied to assess their binding to normal and leukemic cells. Using the alkaline phosphatase antialkaline phosphatase technique, these antibodies were applied to sections of normal organs and to peripheral blood and bone marrow films from hematologically normal individuals and patients with hematologic malignancies. In control experiments, antibodies showed reactivity with cytoplasmic constituents of granulocytes from the promyelocytic to the neutrophilic stage. In acute myeloid leukemia, antibody K101 was positive (more than 20% of blasts) in 13 of 21 (62%) cases, while antibody D46 was positive in 11 of 17 (65%) cases. Antibody H36/71 was positive in only 4 of 24 (17%) cases of acute myeloid leukemia. At least one marker was present in 6 of 8 (75%) cases of acute lymphoblastic leukemia with myeloid antigen-positive blasts and was negative in 20 cases of acute lymphoblastic leukemia with myeloid antigen-negative blasts. These results support the view that abnormal granules (with defective expression of the D46, K101, and H36/71 antigens) form in blastic and leukemic cells of patients with acute myeloid leukemia. Data also suggest that membrane components of myeloid granules are made in the cytoplasm of cells from some acute lymphoblastic leukemia patients with myeloid antigen-positive blasts.

Antibodies, Monoclonal↗

PubMed1992

Immunophenotypic subclassification of chronic lymphocytic leukaemia (CLL).

To determine the significance of the immunophenotypic heterogeneity of B-cell chronic lymphocytic leukaemia (CLL), surface immunoglobulins (SIgs), mouse rosette assays (MR), and a panel of monoclonal antibodies for B cells, T cells and myeloid cells were performed on peripheral blood samples from 61 newly diagnosed cases. Four groups were observed: group I (SIg+, MR+, CD19/20+, CD5+, T antigen (Ag)-; 27 cases); group II (SIg+, MR+, CD19/20+, CD5+, T Ag+; 17 cases); group III (SIg+, MR+ CD19/20+, CD5-, T AG-; 12 cases); and group IV (SIg-, MR+, CD19/20+, Cd5+, T Ag-; 5 cases). Groups were compared according to French-American-British Cooperative Group subtypes, clinical and laboratory features, Rai staging, and survival. Typical CLL morphology (greater than 90% small lymphocytes) was present in 20/20 (100%) of group I cases and 23/27 (85%) group II, III and IV cases (P = 0.09). Expression of a myeloid antigen was seen in 5/27 group I cases (18%) and 1/16 group II cases (6%), but was not predictive of survival (P = 0.36). The CD5- group III had a lower haemoglobin level (P less than 0.0001), higher Rai stage (P less than 0.002), and poorer survival at 5 years (P less than 0.02) than the other groups. We conclude that at least four distinct immunophenotypic subgroups of B-cell CLL can be determined. Expression of myeloid or T-cell antigens does not appear to predict for patient survival; however, lack of CD5 antigen may be associated with more advanced stage of disease and poor patient survival.

Adult↗

PubMed1991

Significance of aberrant immunophenotypes in childhood acute lymphoid leukemia.

Leukemic cells from 51 pediatric patients (younger than 18 years) diagnosed with acute lymphoid leukemia by standard morphologic and cytochemical methods were subjected to flow cytometric studies using a panel of monoclonal antibodies against T-cell (CD1, 2, 3, 4, 5, 7, 8), B-cell (CD10, 19, 20, 21), myeloid (CD13, 14, 15, 33), and HLA-DR antigens. Cases of "conventional" acute lymphoid leukemia (leukemic cells with a normal configuration of B-cell or T-cell differentiation antigens) were observed in 26 of 51 (51%) cases, whereas cases of "aberrant" acute lymphoid leukemia (cells with abnormal patterns of B-cell or T-cell antigens or with concomitant myeloid antigens) were noticed in 25 (49%) cases. Myeloid antigen-positive acute lymphoid leukemia was observed in the leukemic cells of eight (16%) individuals. No significant differences were observed between conventional and aberrant ALL in the distribution of sex, age, leukocyte count, hemoglobin concentration, platelet count, blast count, French-American-British (FAB) type, lymphadenopathy, organomegaly, rate or duration of remission, or survival. When only myeloid antigen-positive cases were compared with myeloid antigen negative-cases, no significant correlations were observed except for duration of first remission (myeloid antigen positive, 26+ +/- 22 months; myeloid antigen negative, 40+ +/- 18 months; P less than 0.001), and duration of survival (myeloid antigen positive, 27+ +/- 24 months; myeloid antigen negative, 62+ +/- 17 months; P = 0.001). These data suggest that pediatric patients with ALL blasts possessing myeloid antigens may represent a high-risk group for length of remission and survival.

Adolescent↗

PubMed1991

Prognostic value of lymphocyte surface markers in acute myeloid leukemia.

We studied the expression of cell surface antigens associated with myeloid and lymphoid leukemias on bone marrow-derived blast cells from 339 patients with newly diagnosed de novo acute myeloid leukemia (AML) enrolled on Cancer and Leukemia Group B (CALGB) chemotherapy protocols. Surprisingly, of 211 cases studied for the expression of CD2 (T-cell marker, sheep erythrocyte binding receptor for T lymphocytes) 45 were positive (21%). In addition, of 298 patients studied for CD19 (B-lymphocyte marker), 41 were positive (14%). Overall, of 170 patients studied for both CD2 and CD19, 56 (33%) were positive. Interestingly, central review of the French-American-British (FAB) morphology of the CD2- and CD19-positive cases showed that FAB M3 was twice as frequent, and M4E eight times as frequent compared with the CD2- and CD19-negative cases. Of 22 lymphocyte antigen-positive cases in which cells were available for studies of Ig or T-cell antigen receptor (TCR) gene rearrangement, 20 were germline, one had a rearranged Ig heavy chain gene, and one had rearranged TCR beta and Ig heavy chain genes. The presence of messenger RNA for CD2 was demonstrated in four CD2 surface antigen-positive cases, thus validating the cell surface data. Lymphocyte antigen-positive cases had karyotypes commonly seen in AML; 71% of cases with an abnormal clone had t(8;21)(q22;q22), inversion 16(p13q22), t(15;17)(q22;q12), or t(9;11)(p22;q23). The patients with lymphocyte markers had a significantly higher incidence of these karyotypic abnormalities compared with patients with lymphocyte antigen-negative AML (34% v 15%, P less than .02). When the outcome to therapy of the lymphocyte antigen-positive cases was compared with that for the CD2, CD19-negative cases, we found that the CD2, CD19-positive cases actually had higher complete remission rates (75% v 59%, P = .04), and significantly longer time to failure (P = .02; 32.4% +/- 6.0% v 18.0% +/- 4.1% at 2 years) and overall survival (P = .02; 43.5% +/- 6.3% v 26.0% +/- 4.5% at 2 years). CD2 antigen-positive cases also had a significantly superior survival (P = .02; 43.8% +/- 7.9% v 29.8% +/- 3.8% at 2 years). There were no significant differences (P less than or equal to .05) between the two groups in age, leukocyte count at diagnosis, incidence of extramedullary disease, or FAB classification.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1991

Immunophenotyping of non-Hodgkin's lymphomas in paraffin-embedded tissue sections. A comparison with genotypic analysis.

Several monoclonal antibodies (MoAbs) are now available for immunophenotyping non-Hodgkin's lymphomas (NHLs) in paraffin-embedded tissue sections. To determine the reliability of these reagents in predicting the genotype, 44 cases of NHL were studied with the alkaline phosphatase-anti-alkaline phosphatase technique with the use of the following MoAbs: leukocyte common antigen (CD45), Mac 387, L26, 4KB5, MB1, MB2, LN2, UCHL1, MT1, and MT2. The lineage of the neoplastic cells was determined in all cases by gene rearrangement studies for immunoglobulin heavy chain and for the T-cell receptor beta-chain. Genotypic results showed B-cell lineage in 33 cases (75%), T-cell lineage in 6 cases (14%), and mixed or undetermined lineage in 5 cases (11%). A concordance of lineage assignment by paraffin section immunophenotyping with gene rearrangement studies was observed in 37 of 39 (95%) lymphomas with an unequivocally defined genotype. MoAb L26 was the most sensitive in detecting B-cell genotype; MoAbs MT1 and UCHL1 were the most sensitive and specific, respectively, in detecting T-cell genotype. The authors conclude that lineage assignment of NHLs in paraffin sections is reflective of the corresponding genotype when an appropriate panel of MoAbs is used.

Antibodies, Monoclonal↗

PubMed1991

Pathology and immunology of adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma is a disseminated malignancy of T lymphocytes infected by the human T-lymphotrophic virus type I. It is endemic in southern Japan, the Caribbean basin, the southeastern United States, and central Africa. The virus is transmitted through intimate contact or exposure to blood products; only a small proportion of those infected develop adult T-cell leukemia/lymphoma. The malignant cells are activated T-helper cells that have suppressor function and multiple cytogenetic abnormalities. The disease occurs in mid to late life, years after exposure to the human T-lymphotrophic virus type I, with hypercalcemia, skin involvement, lymphadenopathy, hepatospenomegaly, lytic bone lesions, and leukemia. Although the disease usually has a rapidly progressive clinical course, there is a spectrum of clinical and pathologic features with smoldering and subacute forms. Our knowledge of this malignancy has grown rapidly and is leading to greater understanding of the relationships between human retroviruses and oncogenes.

Adult↗

PubMed1991

The effects of postinduction intensification treatment with cytarabine and daunorubicin in adult acute lymphocytic leukemia: a prospective randomized clinical trial by Cancer and Leukemia Group B.

Cancer and Leukemia Group B undertook a randomized trial of intensification treatment in adults aged 15 to 79 years with acute lymphocytic leukemia (ALL) in complete remission (CR). Daunorubicin (DNR), prednisone, vincristine (VCR), intrathecal (IT) methotrexate (MTX), and asparaginase produced 177 CRs in 277 patients. One hundred fifty-one patients were randomly assigned to receive treatment as follows: 74 received intensive cytarabine and DNR, and 77 received cycles of mercaptopurine (6-MP) and MTX, followed by 6MP, MTX, VCR, and prednisone for 3 years in all. One hundred twelve patients received CNS prophylaxis. Intensification produced major myelosuppression but did not improve remission duration (median, 21 months). Of the 151 patients with CRs who entered the intensification phase, 29% remain in continuous CR (43 to 117 months); in 19 patients, CRs have lasted for longer than 7 years. No relapses occurred after 60 months. Median survival from the time of randomization was 30 months. Those under 30 years of age responded more frequently, with longer CR and survival. While 53% of those aged 15 to 19 years remain in continuous CR, 92% of patients over 59 years have relapsed. The presence of a myeloid antigen on the leukemic cells was adversely prognostic for CR achievement and for survival. Pretreatment WBC and platelet levels independently affected CR duration and survival. Early M1 marrow development presaged longer remissions. CNS relapse occurred in 47 of 256 patients with normal CSF before treatment, in 29 before CNS prophylaxis. CNS disease occurred after CNS prophylaxis in 18 patients: 13 of 61 who had received standard premaintenance and five of 51 who received intensification. No advantage in CR duration or survival resulted from intensive treatment with DNR and cytarabine following induction of CR.

Adolescent↗

PubMed1990

Trisomy 13: a new recurring chromosome abnormality in acute leukemia.

A new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia. These eight patients had trisomy 13 as the sole cytogenetic abnormality. On central morphologic review, five cases were classified as subtypes of acute myeloid leukemia, one as acute mixed lymphoid and myeloid leukemia, one as acute lymphoid leukemia, and one as acute undifferentiated leukemia. Blasts of all eight cases expressed one or more myeloid differentiation antigens. Three also expressed T-lineage-associated antigens; however, none of these had rearrangement of the T-cell receptor beta, gamma, or delta genes. Four of six cases tested were TdT positive. All eight patients with trisomy 13 were treated with intensive induction chemotherapy; only three entered a short-lived complete remission. Survival of patients with trisomy 13 ranged from 0.5 to 14.7 months, and was significantly shorter than that of the remaining patients (median 9.5 v 16.2 months, P = .007). We conclude that trisomy 13 is a rare, recurring clonal chromosome abnormality in acute leukemia associated with a poor prognosis. Malignant transformation of an immature hematopoietic precursor cell is suggested by the expression of antigens characteristic of both the myeloid and lymphoid lineage, the high incidence of TdT positivity, and the morphologic heterogeneity in these leukemias.

Acute Disease↗

PubMed1990

Induction of differentiation in blast cells and leukemia colony-forming cells from patients with acute myeloid leukemia.

The characteristic lesion in acute myeloid leukemia (AML) is the failure of myeloid cells to differentiate normally, leading to the accumulation of immature blast cells (BC) in the bone marrow. We determined whether BC and leukemia colony-forming cells (L-CFC) from AML patients could differentiate in vitro after short-term culture with interferon-gamma (IFN gamma), 1,25 dihydroxyvitamin D3 (D3), retinoic acid (RA), tumor necrosis factor-alpha (TNF alpha), and granulocyte-monocyte colony-stimulating factor (GM-CSF). Expression of myeloid differentiation antigens CD15, CD14, CD33, and p124 was determined on the BC by immunofluorescence and on the L-CFC by monoclonal antibody (MoAb) and complement (C')-mediated cytotoxicity followed by cloning in methylcellulose. We found that 26 of 39 (67%) cases demonstrated changes in the expression of myeloid differentiation antigens on the BC, and 6 of 7 (86%) cases showed an altered L-CFC myeloid antigen phenotype after short-term culture with differentiating agents. Alterations in myeloid antigen expression in the L-CFC population correlated with a reduction in L-CFC cloning potential. In the BC, alterations of myeloid differentiation antigens occurred in a manner consistent with those observed during normal myelopoiesis. For example, CD14 antigen expression (a late-stage monocyte antigen) increased on BC from 12 of 39 (31%) cases, and p124 (an antigen expressed both by myeloid progenitor cells and by a subset of monocytes) increased on 15 of 39 (38%) cases. Changes in the expression of CD33 antigens (expressed normally by myeloid progenitor cells and by mature monocytes) on the BC were variable, with 7 of 29 cases (24%) showing a decrease and 7 of 29 cases (24%) showing an increase. When comparisons were made between pairs of differentiation agents that caused the altered expression of an antigen on either the BC or L-CFC of a patient, the majority of changes were in the same direction (either both "increased" or both "decreased"). This suggests that the direction of antigen change is characteristic of the leukemia cell subpopulation for each patient and not of the stimulatory agent. This study demonstrates that cells from more than two thirds of AML cases examined responded to various differentiation agents in vitro as measured by changes in the expression of myeloid cell-associated surface antigens and by alterations in cloning potential of the L-CFC, a finding of potential clinical significance.

Antigens, CD↗

PubMed1990

Immunophenotyping of acute leukemias using paraffin-embedded tissue sections.

In a study of 55 patients with either acute lymphoid leukemia (ALL; 25 cases) or acute myeloid leukemia (AML; 30 cases), paraffin-embedded bone marrow particle sections were examined with a panel of monoclonal and polyclonal antibodies reactive toward lymphoid and myeloid-associated antigens, using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique. All cases were previously classified according to the French-American-British (FAB) Co-operative Group, and cases of ALL were immunophenotyped by flow cytometry. Results indicated that myeloid-associated antibodies (Mac 387, KP 1 [CD68], antielastase, antilactoferrin, and antilysozyme) did not react with any case of ALL, M1-AML, or M6-AML, whereas at least one of these antibodies reacted with 20 of 21 (95%) cases of M2, M3, M4, and M5-AML. Anti-glycophorin C marked cases of M6-AML, whereas anti-CD3 labeled T-cell ALL. None of the antibodies tested specifically identified cases of B-cell ALL. The authors conclude that use of a selected panel of antibodies on paraffin-embedded bone marrow particle sections may be of value in the diagnosis and immunophenotypic classification of many cases of acute leukemias.

Acute Disease↗

PubMed1990

The use of cytochemical procedures in the diagnosis and management of acute and chronic myeloid leukemia.

The use of Wright-Giemsa-stained smears alone for the classification of acute leukemias often proves unsatisfactory. Some cases of M1, M5a, M7, and L2 are morphologically similar. In such cases, cytochemical stains can provide an inexpensive and available diagnostic tool. M1 is positive for SBB and MPO. M5a is usually NSE positive, whereas SBB and MPO are negative. M7 usually is ANA esterase, PAS, and AP reactive, and do not stain with SBB, MPO, and ANB esterases. The megakaryocytic lineage usually is confirmed by ultrastructural cytochemistry for PPO or immunocytochemistry for platelet glycoproteins and von Willebrand factor. PAS block positivity and AP dotlike reactivity are suggestive of lymphoid lineage. NSE stains are useful in differentiating M2 from M4. Morphologic and cytochemical techniques also can suggest the presence of certain chromosomal abnormalities such as t(8;21) and inv(16), which may have an influence on prognosis. Because not all cases of acute leukemia are easily subtyped by morphology and cytochemistry, immunophenotyping, karyotyping, and molecular analysis of DNA and RNA of leukemia cells also may be required to define cell lineage.

Azo Compounds↗

PubMed1990

Immunophenotyping of hematologic neoplasms in paraffin-embedded tissue sections.

Several immunohistochemical methods are now available for the staining of neoplastic cells in tissue sections. The authors have found that the alkaline phosphatase-anti-alkaline phosphatase (APAAP) method is sensitive and reliable. Murine monoclonal or nonmurine polyclonal antibodies can be used to label a variety of membranous and/or cellular constituents in tissues that have been routinely processed in a histopathology laboratory. The monoclonal antibody against leukocyte common antigen (CD45) can be used to differentiate hematologic from nonhematologic tumors. Monoclonal antibodies (L26, LN1, LN2, LN3, MB1, MB2) label B-cell lymphomas, whereas other monoclonal antibodies (UCHL1, MT1) more characteristically stain T-cell lymphomas. Polyclonal antibodies against CD3 specifically mark neoplastic cells from T-cell lymphomas and leukemias but as yet are not commercially available. Monoclonal antibodies Leu-M1 (CD15), Ber H2 (Ki-1; CD30), and LN2 label Reed-Sternberg cells from most cases of nodular sclerosis, mixed cellularity, and lymphocyte-depleted Hodgkin's disease. Monoclonal antibodies Mac 387, KP1 (CD68), and NP57 (antielastase), as well as polyclonal antibodies against lysozyme, help identify subtypes of acute myeloid leukemia and extramedullary myeloid cell tumors. Although there are now excellent reagents ready for use, there is still a significant need for more lineage-specific (particularly against CD epitopes) monoclonal antibodies capable of labeling neoplastic cells in paraffin-embedded tissue sections from patients with hematologic malignancies.

Acute Disease↗

PubMed1990

Granulocytic sarcoma.

Granulocytic sarcoma is a variant presentation of acute myeloblastic leukemia, occurring in extramedullary locations. It is uncommon, but it may occur at any site and at any age, which necessitates its inclusion in the differential diagnosis of all undifferentiated tumors. Histology, touch-imprint cytology, cytochemistry, immunocytochemistry, electron microscopy, and molecular studies all contribute to the diagnosis.

Diagnosis, Differential↗

PubMed1989

Expression of the three myeloid cell-associated immunoglobulin G Fc receptors defined by murine monoclonal antibodies on normal bone marrow and acute leukemia cells.

Monoclonal antibodies (MoAbs) have been prepared recently that recognize the three cell-surface receptors for the Fc portion of immunoglobulin (Ig), termed Fc gamma RI (MoAb 32.2), Fc gamma R II (MoAb IV-3), and Fc gamma R III (MoAb 3G8) that are expressed on selected subsets of non-T lymphocyte peripheral blood leukocytes. In the blood, Fc gamma R I is expressed exclusively on monocytes and macrophages, Fc gamma R II on granulocytes, mononuclear phagocytes, platelets, and B cells, and Fc gamma R III on granulocytes and natural killer (NK) cells. We have examined the expression of these molecules on normal bone marrow (BM) cells and on leukemia cells from the blood and/or BM in order to determine their normal ontogeny as well as their distribution on leukemic cells. BM was obtained from six normal volunteers and from 170 patients with newly diagnosed acute leukemia. Normal BM cells were found to express Fc gamma R I, II, and III with the following percentages: 40%, 58%, and 56%, respectively. Cell sorting revealed that both Fc gamma R I and Fc gamma R II were detectable on all subclasses of myeloid precursors as early as myeloblasts. Cell sorting experiments revealed that 66% of the granulocyte-monocyte colony-forming cells (CFU-GM) and 50% of erythroid burst-forming units (BFU-E) were Fc gamma R II positive with only 20% and 28%, respectively, of CFU-GM and BFU-E were Fc gamma R I positive. Acute myeloid leukemia (AML) cells expressed the three receptors with the following frequency (n = 146): Fc gamma R I, 58%; Fc gamma R II, 67%; and Fc gamma R III, 26% of patients. Despite the fact that Fc gamma R I is only expressed on monocytes among blood cells, AML cells without monocytoid differentiation (French-American-British [FAB]M1, M2, M3, M6) were sometimes positive for this receptor. However, Fc gamma R I was highly correlated with FAB M4 and M5 morphology (P less than .001). Fc gamma R II was also correlated with FAB M4 and M5 morphology (P = .003). Cells from 11 patients with acute lymphoblastic leukemia were negative for Fc gamma R I, but six cases were positive for Fc gamma R II and III (not the same patients). These studies demonstrate that Ig Fc gamma R are acquired during normal differentiation in the BM at or before the level of colony-forming units. In addition, we show that acute leukemia cells commonly express Fc gamma R.

Acute Disease↗