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)

Glycosphingolipids (GSLs) are complex macromolecules on cell membranes that have been shown to play a role in neutrophil differentiation, activation, phagocytosis, and adhesion to both microorganisms and vascular endothelium. Because GSLs are often cryptic antigens on cell membranes, little is known regarding GSL expression in early myelopoiesis. To study the latter, myeloblasts were collected from patients with acute nonlymphocytic leukemia (ANLL) who required therapeutic leukocytopheresis for hyperleukocytosis. The neutral GSLs were isolated and identified by high-performance thin-layer chromatography (HPTLC), HPTLC immunostaining, gas chromatography, nuclear magnetic resonance, and fast atom bombardment-mass spectrometry. Like mature peripheral blood neutrophils, myeloblasts expressed glucosylceramide, lactosylceramide, and the neolacto-family GSLs, lactotriaosylceramide and neolactotetraosylceramide. Unlike neutrophils and chronic myeloid leukemia, most ANLL samples also expressed the globo-series GSLs, globotriaosylceramide and globotetraosylceramide. Globo GSL expression was strongly associated with a myeloblastic (ANLL M0-M2) and monoblastic phenotype (M5). A weak association was also noted with expression of either lymphoid (P <.10) or early hematopoietic markers (terminal deoxynucleotidyl transferase [TdT], CD34; P <.10). Globo-positive ANLL samples bound both shiga toxin and parvovirus B19 on HPTLC immunostaining. Based on these findings, we propose that neolacto and globo GSLs are expressed during early myeloid differentiation. Globotriaosylceramide expression on myeloblasts, and possibly myeloid stem cells, may have important implications for the use of shiga toxin as an ex vivo purging agent in autologous stem cell transplantation. Expression of globotetraosylceramide, the parvovirus B19 receptor, on myeloblasts may also explain the association between B19 infection, aplastic anemia, and chronic neutropenia of childhood.
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PMID:Glycosphingolipid expression in acute nonlymphocytic leukemia: common expression of shiga toxin and parvovirus B19 receptors on early myeloblasts. 1239 13

Hematopoietic neoplasm coexpressing CD4 and CD56 includes a subset of acute myeloid leukemia with myelomonocytic differentiation, plasmacytoid monocyte tumor, and other immature hematopoietic neoplasms of undefined origin. Herein, we report a CD4+CD56+CD68+ hematopoietic tumor that was thought to be a tumor of plasmacytoid monocytes. This case is unique in the absence of accompanying myelomonocytic leukemia and the faint expression of cCD3 on the tumor cells. The patient was a 22-yr old man presented with multiple lymphadenopathy and an involvement of the bone marrow. Tumor cells were large and monomorphic with an angulated eosinophilic cytoplasm of moderate amount. Nuclei of most tumor cells were eccentric and round with one or two prominent nucleoli. Rough endoplasmic reticulum was prominent in electron microscopic examination. Tumor cells expressed CD4, CD7, CD10, CD45RB, CD56, CD68, and HLA-DR and were negative for CD1a, CD2, sCD3, CD5, CD13, CD14, CD20, CD33, CD34, CD43, CD45RA, TIA-1, S-100, and TdT. cCD3 was not detected in the immunostaining using paraffin tissue, but was faintly expressed in flow cytometry and immunostaining using a touch imprint slide. T-cell receptor gene rearrangement analysis and EBV in situ hybridization showed negative results. Cytochemically, myeloperoxidase, Sudan black B, and alpha naphthyl butyrate esterase were all negative.
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PMID:CD4+CD56+CD68+hematopoietic tumor of probable plasmacytoid monocyte derivation with weak expression of cytoplasmic CD3. 1248 12

We investigated the prognostic relevance of immunophenotype and other clinical pathological features in 379 adult patients with de novo (acute myeloid leukemia) AML diagnosed and treated at our institution during an 8-year period. Acute promyelocytic leukemia (APL) cases were excluded because they received different treatment. The overall complete remission (CR) rate post-induction therapy with Ara-C and daunorubicin (DNR) was 60% with a median disease free survival (DFS) of 72 weeks, and a median overall survival (OS) of 54 weeks. At diagnosis, CD34, deoxynucleotidyl transferase (TdT), CD7, CD56, HLADR and CD19 were expressed in 65, 19, 32, 15, 87 and 5%, respectively, of 379 evaluable cases. CD34 positive patients had a significantly lower CR rate (P=0.0003) than CD34 negative patients and there was a trend to a lower remission rate in HLADR positive patients (P=0.067). In multi-variate analysis, co-expression of CD34 and HLADR was an independent adverse factor for achieving CR (P=0.0364). CD56 expression was associated with a significantly shorter overall survival (P=0.0262), but did not affect remission rate or disease free survival. Neither TdT nor CD7 expression was associated with treatment outcome. Age (60 years or older) and cytogenetic features (classified by favorable, intermediate and unfavorable groups) were associated with a lower CR rate, shorter disease free survival and shorter OS. Patients with higher white cell counts (WBC) also had a significantly lower remission rate (P=0.0064) and OS (P=0.0127). We propose a prognostic score for achieving CR in AML patients based on age, WBC, cytogenetics and CD34/HLADR status as four independent factors. Defined by number of factors, this score system may help to stratify AML patients to alternative treatment for better outcome.
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PMID:Prognostic relevance of immunophenotyping in 379 patients with acute myeloid leukemia. 1463 79

The rare hypocellular variants of acute leukemia (AL) previously also termed smouldering leukemia, almost always exhibit myeloid differentiation. Very rare cases of hypocellular AL with lymphoid differentiation have been reported, usually in children. This paper describes two cases (an 87-year-old woman and a 79-year-old man) in whom the blood findings were suggestive of AL. Paraffin-embedded bone marrow biopsy specimens revealed similar findings in both patients: there was severe hypocellularity, the cells of normal hemopoiesis were greatly reduced in number, and there was a diffuse increase in blast cells, which represented more than 50% of nucleated marrow cells. The blasts coexpressed TdT and CD34 and were negative for myeloperoxidase, CD117, CD68 and naphthol AS-D chloroacetate esterase. For the first time immunohistochemical Pax-5/CD34 doublestainings are provided, which revealed the blasts in one case to coexpress Pax-5 and CD34. All the blasts were CD79a-positive and 20% were also CD10-positive. In the other case, 20% of the blasts were CD79a-positive, 30% coexpressed Pax-5 and CD34 by doublestaining, and showed a clonal rearrangement of the immunoglobulin heavy chain gene. Thus a diagnosis of AL of lymphoid lineage, hypocellular variant, was made on the basis of immunohistochemical findings. The clinical course appears to be similar to that of hypocellular AML, as neither patient has developed overt leukemia during the one-year follow-up period.
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PMID:Adult hypocellular acute leukaemia with lymphoid differentiation. 1469 36

We describe a case of a patient with CD34+, TdT+, CD13-, CD33-, MPO- undifferentiated acute leukemia who refused chemotherapy and who achieved complete hematological remission 14 months after the diagnosis, during a short course of granulocyte-colony stimulating factor (G-CSF) for neutropenia and life threatening infection. Relapse occurred approximately one year later and G-CSF was reintroduced, being maintained for 4 months, at a dose and frequency adapted to maintain normal blood counts, a complete hematological remission being achieved again. Five months after withdrawing the G-CSF therapy a second relapse was observed; G-CSF was tried again with success, resulting in a very good hematological response that was sustained by G-CSF maintenance therapy. One year latter there was the need of increasing the doses of G-CSF in order to obtain the same hematological effect, at same time blast cells acquired a more mature CD34+, TdT-, CD13+, CD33-, MPO+ myeloid phenotype. Finally, the patient developed progressive neutropenia, anemia, thrombocytopenia and acute leukemia in spite of G-CSF therapy, dying 64 months after initial diagnosis (50 months after starting G-CSF therapy) with overt G-CSF resistant acute myeloblastic leukemia (AML), after failure of conventional induction chemotherapy.
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PMID:Hematological remission and long term hematological control of acute myeloblastic leukemia induced and maintained by granulocyte-colony stimulating factor (G-CSF) therapy. 1495 60

Acute promyelocytic leukemia (APL) is a subtype acute myeloid leukemia in which leukemic promyelocytes predominate in the bone marrow (BM). Rapid diagnosis is critical for treatment decision since all-trans-retinoic acid must be administrated promptly. The microgranular variant may be of difficult diagnosis, as it may be confused with other diseases on morphological grounds. The purpose of this study was to determine if the microgranular variant has the same antigenic profile as the classical hypergranular type. The immunophenotype of leukemic cells from the bone marrow of 50 patients, with the PML-RARalpha gene rearrangement confirmed by RT-PCR, was determined by flow cytometry using a large panel of 22 monoclonal antibodies and a polyclonal anti-TdT antibody. Thirty-four cases were classified as classical APL and 16 as microgranular APL. The immunophenotypic profile of the two subtypes was indistinguishable concerning the presence or absence of these antigens, including the absence of reactivity for the HLA-DR antigen. The simultaneous immunophenotypic combination of a unique major cell population, heterogeneous intensity of expression of CD13, and the typical pattern of CD15/CD34 expression were similarly present in the hypergranular and microgranular subtypes. Homogeneous expression of CD33 was observed in 76% of the classical APL cases and in 100% of the microgranular cases. Additionally, we have studied two cases of PLZF-RARalpha APL that also displayed the same immunophenotype described for classical APL. Thus, the immunophenotypic profile highly characteristic of the PML-RARalpha gene rearrangement was also observed in microgranular and PLZF-RARalpha variants of APL.
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PMID:Microgranular and t(11;17)/PLZF-RARalpha variants of acute promyelocytic leukemia also present the flow cytometric pattern of CD13, CD34, and CD15 expression characteristic of PML-RARalpha gene rearrangement. 1511 96

We evaluated the frequency and prognostic significance of extramedullary infiltrates (EMI) at presentation of acute myeloid leukemia (AML) in adult patients. Of 331 cases with de novo AML, 101(30.5%) had extramedullary infiltrates at diagnosis. The extramedullary manifestations included: lymphadenopathy, splenomegaly, hepatomegaly, gingival hypertrophy, skin infiltrates and involvement of central nervous system (CNS). Patients with EMI had a high initial WBC count and a high proportion of M4/M5 morphological variants. The complete remission rate (CR) with induction chemotherapy was lower in patients with EMI (P=0.0077) and their overall survival was also inferior (P=0.0017). Flow cytometric evaluation of the surface antigens expressed by the leukemic blasts for CD34, TdT, HLADR, CD7, CD19 and CD56 found that only CD56 expression was associated with EMI. The association of CD56 expression with lymphadenopathy was statistically significant (P=0.035). Abnormal karyotypes were found in 50.6% of patients with EMI and 49.7% of patients without EMI. Only 11q23 abnormalities were associated with specific sites of EMI; lymphadenopathy (P=0.0111) and gingival hypertrophy (P=0.0016). Our study of adult AML patients demonstrates that EMI at diagnosis is associated with CD56 expression by leukemic blasts, 11q23 karyotypic abnormalities, low complete remission rate and poor overall survival.
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PMID:Extramedullary infiltrates of AML are associated with CD56 expression, 11q23 abnormalities and inferior clinical outcome. 1528 11

Early plasmacytoid dendritic cell (pDC) leukemia/lymphoma has recently been described as a CD4(+)CD56(+) lineage negative malignancy with characteristic clinical, morphologic, immunophenotypic, and biological features. We present a case of a 72-year-old man who was diagnosed with isolated skin involvement 30 months ago and received numerous chemotherapy cycles that did not prevent three relapses of the disease, the last two involving the bone marrow. The bone marrow was nearly completely infiltrated with small- to medium-sized blasts displaying a high nuclear to cytoplasmic ratio, a cytoplasm with faint basophilia lacking granulations or Auer rods. Small vacuoles surrounding the nucleus were frequently observed. Flow cytometry showed CD4(+), CD56(+), CD45(+), CD38(+), HLA-DR(+), CD33(+), CD123(+), CD2(-), cyCD3(-), CD7(-), CD10(-), CD11b(-), CD13(-), CD14(-), CD16(-), CD19(-), cyCD22(-), CD24(-), CD34(-), CD57(-), CD61(-), CD64(-), CD65(-), cyCD79a(-), CD117(-), MPO(-), and TdT(-) population. At the second bone marrow relapse, CD117 was also positive. Our patient was initially treated with acute myeloid leukemia-type chemotherapy, later he was given acute lymphoblastic leukemia-type treatment, and at the last relapse he received CHOP chemotherapy. Each treatment led to rapid response of tumor manifestations with disease-free intervals of 7 months, 9 months, and 8 months, respectively. Although patients usually have an ominous prognosis, with only 25% living more than 24 months, our patient is alive after 30+ months and has again achieved complete remission after the last chemotherapy.
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PMID:Early plasmacytoid dendritic cell leukemia/lymphoma coexpressing myeloid antigenes. 1531 55

The apoptosis failure in cytostatic treatment of haemoblastosis is one of the means of chemoresistance. We were interested in the relationship of the after-doxorubicin-treatment-AML cells apoptosis and the immunophenotype, selected clinical and laboratory parameters, and also the P-gp, MRP, LRP, Bcl-2, Bax proteins expression. All analysis were evaluated with the flow cytometry method. To detect apoptotic cells in the sample, we used three methods: annexin test, TUNEL (TdT-mediated dUTP nick end labeling) test, and caspase 8 detection. After the cell cultivation the statisticaly important increase of apoptotic cells in the culture was apparent. The relation between the AML blast in vitro reaction and some clinical parameters such as the age of patient, white blood cell count, and blast percentage was also observed.
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PMID:The multidrug resistance and apoptosis evaluation in acute myeloid leukemia cells after the in vitro doxorubicin treatment. 1556 36

To explore the expression of insulin-like growth factor receptor type I (IGF-IR) and its relationship to apoptosis in hematopoietic cells of MDS and AML marrow, bone marrow nucleated cells from 16 patients with myelodysplastic syndrome (MDS) and 16 patients with acute myeloid leukemia (AML) were collected for analysis, respectively. Another 16 normal donors' marrow samples were taken as controls. Immunocytochemical method (APAAP) and TdT-mediated dUTP nick end labeling (TUNEL) fluorescence were used simultaneously on cytospins of nucleated cells from these patients. Then, the ratios of IGF-IR positive cells and apoptosis cells in all nucleated cells were counted separately. The results showed that (1) there was a higher IGF-IR expression rate (56.8 +/- 14.3)% in nucleated cells of MDS marrow than that in normal marrow (40.4 +/- 9.6)% (P < 0.01). Also IGF-IR positive rate in AML marrow (86.8 +/- 13.8)% was significantly higher than that in normal marrow (P < 0.01). Furthermore, IGF-IR had higher expression in AML marrow when compared to MDS marrow (P < 0.01); (2) apoptosis in nucleated cells of MDS marrow (5.4 +/- 3.0)% was significantly higher than that in normal marrow (1.2 +/- 0.9)% (P < 0.01) and AML marrow (0.3 +/- 0.4)% (P < 0.01), while there was less apoptosis in AML marrow than that in normal marrow (P < 0.01); (3) apoptosis occurred mainly in IGF-IR negative cells (9.0 +/- 4.8)% and less in IGF-IR positive cells (1.4 +/- 2.4)% (P < 0.01). IGF-IR expression showed negative correlation with apoptosis (r = -0.852, P < 0.01); (4) IGF-IR of MDS nucleated cells in RAEB/RAEB-t/CMML expressed higher than that in RA/RAS (64.1 +/- 3.2% vs 53.5 +/- 16.2%) subgroup, although no significant difference was found (P > 0.05); and apoptosis in RAEB/RAEB-t/CMML subgroup was lower than that in RA/RAS cases (3.1 +/- 2.1% vs 6.4 +/- 2.8%) (P < 0.05); (5) IGF-IR positive rate in nucleated cells of MDS and AML marrow showed positive correlation with blast rate (r = 0.677; P < 0.01). It is concluded that there is overexpression of IGF-IR in marrow nucleated cells in MDS and AML cases. And it seems that the overexpression of IGF-IR may suggest some malignant proliferation tendency and suppress cell apoptosis through some mechanism in these malignant hematologic ailments. So, anti-IGF-IR will become a new approach for therapy of MDS and AML.
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PMID:[Expression of insulin-like growth factor receptor type I in marrow nucleated cells from hematologic malignancies and its anti-apoptotic effect]. 1597 47


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