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

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

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

It has been suggested that cord blood T cells may be less able to mediate GVHD than marrow-derived T cells due to their naive status. A decreased potential for GVHD may be advantageous for allogeneic transplant, but this benefit might be counteracted by loss of the GVHD associated graft-versus-leukemia (GVL) effect. The GVL potential of cord blood could be doubly compromised since cord blood NK cell activity is also decreased. To assess these issues we have performed extensive comparative functional and immunophenotypic evaluations of cord and adult mononuclear cells. We found a somewhat reduced alloproliferative, allostimulatory and allocytolytic capacity of cord blood mononuclear cells in bulk assays but not by limiting dilution assays. Immunophenotyping revealed no significant differences in the proportion of major lymphocyte subsets with the exception of the previously recognized predominance of CD45RA+ cells in both CD4 and CD8 cord blood T cells. Cord blood T cells expressed normal percentages of the cellular adhesion molecules, CD11a, CD18 and LFA-3; however, the antigen density of each of these molecules was less than that found on adult T cells. Fewer resting cord blood T cells expressed CD54, the ligand for LFA-1. Cord blood B cells and monocytes expressed normal levels of HLA-class I and HLA class II DR, DP and DQ antigens, suggesting that the decreased expression of cellular adhesion molecules or their receptors rather than a decrease in expression of HLA might have contributed to the lower alloreactivity of cord blood. Although the percentages of NK cells and NK cell subsets in adult and cord blood were similar our data confirmed that cord blood has very low NK lytic activity. In contrast, LAK activity was much more readily induced in cord blood compared with adult PBMC, a finding which could be explained in part by a higher frequency of LAK precursors and a more rapid expansion of NK cells in response to culture with medium containing of NK cells in response to culture with medium containing IL-2. Cord blood LAK cells were readily able to lyse fresh leukemia targets from patients with ALL, AML and CML. The data indicate that although the alloreactive potential of cord blood cells may be somewhat decreased, it is not absent and must be considered a factor in cord blood transplants. LAKp with the potential to lyse leukemia are present in increased numbers in cord blood and might contribute to the GVL effect of a cord blood transplant.
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PMID:Characterization of the alloreactivity and anti-leukemia reactivity of cord blood mononuclear cells. 759 66

A portion of patients with acute myeloid leukemia also display surface antigens associated with lymphoid development (Ly+AML). The incidence of Ly+AML varies considerably between independent studies, both overall and with regard to individual antigens. On average, lymphoid-associated antigen expression is relatively low in AML. The reasons for some striking differences between conflicting reports are not clear, but are most probably due to various technical aspects including several arbitrary parameters. The data accumulated from the literature lead to the following conclusions: (i) use of different reagents against the CD surface antigens, different positive/negative cut-off levels, analysis of fresh or frozen cell material and variable sensitivities of the analytical instruments (expression of lymphoid-associated antigens was commonly weaker than myeloid-associated markers) seriously influence the results; (ii) most antigens (CD1, CD2, CD3, CD5, CD8, CD10, CD19, CD20, CD21, CD22) were expressed on less than 10% of AML cases; (iii) the CD4 and CD7 antigens, also found on normal monocytic and immature myeloid progenitor cells, were detected in 24% and 15% of AML cases, and their expression correlated with FAB M4/M5 and M1/M2 morphology, respectively; (iv) differences between pediatric and adult Ly+AML were restricted to CD4 and CD19 expression being detected more often in childhood cases; (v) there is no cytogenetic anomaly specific for Ly+AML; anomalies exclusively associated with lymphoid malignancies were not seen; aberrations involving 11q23, 14q32, and the 9;22 translocation seem to be increased; (vi) in most studies, expression of lymphoid-associated antigens (with the exception of CD7) on AML blasts lacked prognostic significance; CD7+AML appears to be a particular subset of malignant myeloid progenitors. In summary, these findings suggest that in general, Ly+AML may not represent a biologically distinct form of leukemia as these cases have similar clinical features and respond to therapy in a comparable manner.
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PMID:Acute myeloid leukemias expressing lymphoid-associated antigens: diagnostic incidence and prognostic significance. 768 17

MDR1 gene expression was examined in acute leukemia cells from 75 Japanese patients at diagnosis (50 with acute myeloblastic leukemia [AML]: 10 M1, 18 M2, 5 M3, 8 M4, 9 M5; 25 with acute lymphoblastic leukemia [ALL]: 13 B-precursor, 12 T-lineage). The results of MDR1 mRNA expression by reverse transcriptase polymerase chain reaction were confirmed by immunostaining using the anti-P-glycoprotein monoclonal antibody UIC2 and by a functional study using the rhodamine efflux test. Morphologically, AML M1 cases had the highest incidence of MDR1 gene expression (6 of 10 patients). Phenotypically, CD7 and CD34 were the only surface markers that were significantly associated with MDR1 gene expression (P < .01). In CD7+CD4-CD8- ALL, which is thought to originate from the lymphohematopoietic stem cell, expressed the MDR1 gene with a high incidence (six of eight patients), whereas three surface CD3+ and one CD4+CD8+ T-cell ALL (T-ALL) did not have detectable MDR1 transcripts. Only two cases of 13 B-precursor ALL had MDR1 mRNA, one of which had the Philadelphia (Ph1) chromosome. No association was observed between MDR1 gene expression and CD34 positivity in ALL. Our results that MDR1 mRNA was frequently expressed in CD7+ AML and CD7+CD4-CD8- ALL, together with the previous reports indicating clinical similarities between these leukemias, provides a clue to clarify a relationship between CD7+ AML and CD7+CD4-CD8- ALL. In addition, MDR1 expression in CD7+ AML/ALL might be responsible for the poor response to conventional chemotherapies of these types of leukemia.
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PMID:Expression of MDR1 gene in acute leukemia cells: association with CD7+ acute myeloblastic leukemia/acute lymphoblastic leukemia. 769 87

Graft-versus-host disease (GVHD) is a life threatening complication that may occur following allogenic bone marrow transplantation (BMT) in the patients with aplastic anemia, leukemia or genetic immunodeficiency. It has been known that GVHD occurs approximately 70% of recipients of BMT in western countries but no definite incidence has been reported in Korea. In our St. Mary's Hospital, GVHD occurs in about 30% of BMT recipients. Histopathologically the acute phase skin shows diffuse lymphocytic infiltrates in the upper dermis with extensive exocytosis. Scattered throughout the epidermis are many degenerated keratinocytes, which are often associated with one or more satellite lymphocytes (satellite cell necrosis). In the chronic phase, acanthosis, eosinophilic keratinocytes resembling colloid bodies and mononuclear cell infiltrates in the upper dermis are noted. We reviewed 5 cases of acute GVHD and 6 cases of chronic GVHD. All patients received allogenic BMT from Jan. 1, 1992 to July 1, 1993. Ten patients were male and one was female. The mean age was 34 (20-70). The pathologic diagnosis was 3 cases of CML, 2 of ALL, 2 of AML (FAB M2), 2 of aplastic anemia, 1 of CLL and 1 of AML (FAB M5). The interval from BMT to GVHD varied from 14 days to 4 years (median 220 days). The skin and GI tract were involved in all eleven cases. Ten cases were histologically proven by skin biopsies, and two cases by salivary gland and colonic biopsies, respectively. The histological findings of the skin, salivary gland and colonic biopsieds were described. Immunohistochemical stain of the skin was done using CD4, CD8, HLA DR and Leu 7 antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Graft-versus-host disease--clinical and pathological analysis of 11 biopsy proven cases. 770 86

Serial blood and marrow specimens from eight adult recipients of sex-mismatched transplants (BMT) for chronic myeloid leukemia (CML, n = 3), Ewing sarcoma (n = 1), acute myeloid leukemia (AML) in second remission (n = 1), acute lymphatic leukemia (ALL, n = 1) and multiple myeloma (n = 2) were analyzed by the simultaneous immunophenotypic CD3, CD4, CD8, CD20, CD34, CD10 and genotypic analysis (for X and Y chromosomes). This combined technique of moAb/APAAP staining for cell surface and cytoplasmic antigens and fluorescence in situ hybridization (FISH) for the detection of sex chromosomes allowed the qualitative and quantitative evaluation of mixed chimerism and/or relapse. Using the same slides for moAb/APAAP and FISH allowed the simultaneous identification of the cell lineage, the lymphocyte subpopulation and the genotype (XX or YX) in every blood or BM specimen analyzed. A mixed chimerism in the T cell (CD4, CD8+: median 26% host cells, range 5-44%) and in the myelomonocytic cell population (CD14+ median 16% host cells, range 5-50%) was observed at day +7 after BMT. By days +14 to +18 this mixed chimerism was reduced to 18% host T cells (range 5-50%) and 7% host myelomonocytic cells (range 0-20%). Beyond days +21 to +28 a stable donor chimerism for T cells, myelomonocytic cells and granulocytes was observed in seven of eight patients. Still 0.5-1% host cells of different lineages were detectable in five from the eight patients at later time points (> day + 100). In three patients with CML these cells were CD13 or CD13, CD34 positive and in one was CD4, CD8 positive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of mixed chimerism and leukemic relapse after allogeneic bone marrow transplantation in subpopulations of leucocytes by fluorescent in situ hybridization in combination with the simultaneous immunophenotypic analysis of interphase cells. 774 54

At the present time the effectiveness of interleukin-2 (IL-2) administered together with IL-2 in vitro activated lymphocytes (LAK) in the treatment of malignant neoplasias is being assessed. We report the case of an 8 -year- old patient suffering from acute myeloid leukemia (AML) who had relapsed from an autologous bone marrow transplant (ABMT) and received a second ABMT in partial remission. After the second ABMT, the patient, who entered into a phase of complete remission (CR) but with a severe thrombocytopenia, was treated with IL-2 and allogeneic LAK cells obtained from his father. During treatment the lymphocyte subpopulations and cytolytic activity were assayed. Increases in the patient's lymphocytes with CD3- CD4- CD8- CD16+, CD3- CD4- CD8- CD56+, CD3- CD4- CD8+ CD56+ and CD3- CD4- CD8+ CD56+ phenotypes were observed and these were correlated with cytolytic activity measured against the K562 cell line. The patient remained in CR for longer (14 months) than after the first ABMT (5 months). The immune activation produced by this therapy could have had an antileukemic effect in the patient.
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PMID:[Immunotherapy with interleukin-2 and allogenic LAK cells in a patient with acute myeloblastic leukemia]. 775 46

The PEBP2 alpha A and PEBP2 alpha B genes encode the DNA-binding subunit of a murine transcription factor, PEBP2, which is implicated as a T-cell-specific transcriptional regulator. These two related genes share the evolutionarily conserved region encoding the Runt domain. PEBP2 alpha B is the murine counterpart of human AML1, which is located at the breakpoints of the 8;21 and 3;21 chromosome translocations associated with acute myeloid leukemia. Northern (RNA) blots of various adult mouse tissues revealed that the levels of expression of both genes were most prominent in the thymus. Furthermore, transcripts of PEBP2 alpha A and mouse AML1/PEBP2 alpha B were detected in T lymphocytes in the thymuses from day 16 embryos and newborns, as well as 4-week-old adult mice, by in situ hybridization. The expression of the genes persisted in peripheral lymph nodes of adult mice. The transcripts were detected in all the CD4- CD8-, CD4+ CD8+, CD4+ CD8-, and CD4- CD8+ cell populations. The results indicated that both genes are expressed in T cells throughout their development, supporting the notion that PEBP2 is a T-cell-specific transcription factor. Transcripts of mouse AML1/PEBP2 alpha B were also detected in day 12 fetal hematopoietic liver and in the bone marrow cells of newborn mice. The implication of mouse AML1/PEBP2 alpha B expression in hematopoietic cells other than those of T-cell lineage is discussed in relation to myeloid leukemogenesis.
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PMID:Expression of the Runt domain-encoding PEBP2 alpha genes in T cells during thymic development. 786 57

The eradication of minimal residual blast populations by activation of autologous cytotoxic cells with interleukin 2 (IL-2) is a new promising tool in the treatment of acute myelocytic leukemia (AML). However, the immunological effector cells are not yet clearly defined. The present study was designed to investigate the presence of cytotoxic precursor cells in active AML and to identify phenotypical and functional characteristics of autologous anti-leukemic cytotoxic effector cells. For this purpose, mononuclear cells (MNC) containing at least 70% leukemic blasts were isolated from bone marrow of untreated AML and cultured in the presence of 3000 IU/ml recombinant IL-2 (rIL-2) for 6-8 weeks. Under these conditions, T-cells were selected in the bone marrow cultures and overgrew the leukemic blasts. The resulting T-cell populations were cloned by limiting dilution and the clones obtained were characterized for their phenotypical and functional patterns. Totally, cloning resulted in 68 clones and a few cell lines. The clonality was verified by RT PCR analysis of TCR V beta gene expression. All clones obtained stained positive for CD2, CD3, DR and CD56. The vast majority (68%) of T-cell clones/lines was CD4+, a few clones expressed CD8 (19%) or CD4 and CD8, and four clones were of TCR gamma delta origin. Seven of 15 clones tested, including three CD4+, two CD8+ and two TCR gamma delta(+)-clones were found to be cytotoxic against autologous leukemic blast cells. All except one clone expressed oncolytic activities against allogeneic blasts too. One of the TCR gamma delta(+)-clones demonstrated NK activity by lysis of K562 targets. The majority of the T-cell-clones released IL-2, IL-8, TNF-alpha, GM-CSF but only a few IFN gamma and expressed high levels of mRNA for IL-2, TGF-beta and IL-10. None of the clones was found to produce IL-3, IL-4, IL-7 and TNF-beta. The data provide evidence of the existence of T-cell precursors in untreated AML bone marrow differentiating to cytotoxic cells with activity against autologous and allogeneic AML blast cells.
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PMID:Bone marrow-derived T-cell clones obtained from untreated acute myelocytic leukemia exhibit blast directed autologous cytotoxicity. 786 44


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