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)

Recognition of the characteristic cutaneous lesions of disseminated candidiasis may allow earlier diagnosis and treatment of this often fatal fungal infection. The skin lesion developed in patients with hematologic malignancies and compromised host defenses, at a time when they were febrile, clinically deteriorating, and failing to respond to multiple antibiotics. This report discusses two patients with acute myelogenous leukemia with cutaneous manifestations of disseminated candidiasis due to Candida tropicalis. Single or multiple erythematous or purpuric 0.5- to 1-cm papulonodules with pale centers were seen on the trunk and proximal extremities. In most reported cases of disseminated candidiasis with skin lesions, the diagnosis can be confirmed by histologic evaluation of a skin biopsy before appropriate cultures identify the organism.
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PMID:Cutaneous manifestations of disseminated candidiasis. 692 57

Normal cross-reacting antigen, a glycoprotein that shares some antigenic determinants with carcinoembryonic antigen, was consistently demonstrated by tissue immunoperoxidase staining in the cytoplasm of both non-neoplastic and neoplastic neutrophilic granulocytes. It was absent in lymphoid cells, but occasional cells of the macrophage/histiocyte series showed variable staining. Malignant cells from patients who had non-Hodgkin or Hodgkin lymphomas were negative for normal cross-reacting antigen. These findings were in contrast to the findings of specific normal cross-reacting antigen positivity in neoplastic granulocytes from three patients who had acute granulocytic leukemia, three who had chronic granulocytic leukemia, and one who had a granulocytic sarcoma. Similar normal cross-reacting antigen positivity was also seen in granulocytes from two patients who had granulocyte dysplasia. It is suggested that direct tissue visualization of normal cross-reacting antigen using immunoperoxidase technics may be of value in the classification and diagnosis of hematologic malignancies, and may provide an additional marker for cells of the granulocytic series.
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PMID:Direct tissue visualization of normal cross-reacting antigen in neoplastic granulocytes. 698 61

Serum ferritin was measured in a variety of hematologic malignancies at presentation, in remission following therapy, and in relapse. Ferritin was strikingly increased in all acute leukemias at presentation and in relapse, in the blastic crisis of CML, and in smouldering leukemia. Remission in both ALL and ANLL was associated with a reduction of serum ferritin, and this normalization was a function of remission duration. In the malignant lymphomas serum ferritin was related to tumor histology. Highest levels were found in Hodgkin disease and histiocytic lymphoma, normal levels in lymphocytic lymphoma, and intermediate levels in mixed histiocytic-lymphocytic lymphoma. In all cases, remission was associated with normalization of serum ferritin. These correlations suggest that serum ferritin measurements may be of clinical usefulness in the initial evaluation and in the assessment of response to therapy in patients with acute leukemia and malignant lymphoma.
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PMID:Serum ferritin in hematologic malignancies. 700 94

Flow cytometry of cellular DNA content revealed ploidy abnormalities in 15% of 170 patients with various leukemias, in 50% of 26 patients with malignant lymphomas, and in 68% of 110 patients with multiple myeloma, for an overall incidence of DNA content abnormality of 37% in 306 patients with hematologic malignancies. Since the incidence of ploidy abnormality in over 100 solid tumors exceeded 90%. DNA flow cytometry is also ideally suited to screen for bone marrow metastases. Cell separation by centrifugal elutriation was shown to permit enrichment of aneuploid cells, including one example where cells with abnormal DNA content were not recognized in the unfractionated sample. Biparametric measurements of acridine orange-stained cells for DNA and RNA content analysis were suitable to enhance the discriminatory power of flow cytometric detection of lymphoma and myeloma tumor cells in heterogeneous cell populations of bone marrow and lymph nodes. DNA/RNA measurements in leukemia, (the disease category with the lowest incidence of abnormal DNA mode) revealed a markedly higher mean RNA content in acute myeloid leukemia compared with normal or acute lymphoblastic leukemia bone marrow. While these different RNA content patterns were found in whole marrow, cell separation by centrifugal elutriation of normal marrow disclosed cell subpopulations of myeloid precursor cells with a RNA content pattern similar to that of unseparated AML marrow. Hence, the described differences in RNA content between normal and AML marrow seem to be related to the greater heterogeneity of differentiated cells in normal marrow and per se do not appear to be a unique feature of the leukemia disease process.
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PMID:Characterization of hematologic malignancies by flow cytometry. 700 71

We evaluated the effects of transforming growth factor-beta 1 (TGF-beta 1) on the growth of hematopoietic progenitors in normal donors and in patients with hematologic malignancies now designed as clonal disorders of multipotential stem cells. TGF-beta 1 at 80 pM exhibited differential effects on the normal hematopoietic progenitors when cells were stimulated with different growth factors, such as G-CSF, GM-CSF, interleukin-3 (IL-3), or stem cell factor (SCF). The suppressive effect by TGF-beta 1 was increased for growth with GM-CSF, IL-3, and SCF, and growth with G-CSF was unaffected in hematologic malignancies, TGF-beta 1 suppression for growth with G-CSF was increased for essential thrombocythemia (ET) and polycythemia vera; chronic myelogenous leukemia (CML) in chronic phase; CML in accelerated phase; CML in myeloid crisis; myelodysplastic syndrome (MDS) in refractory anemia; MDS in refractory anemia with an excess of blasts; and acute myeloblastic leukemia (AML). In CML-myeloid crisis and AML, TGF-beta 1 almost completely abolished the growth, with some patient-to-patient variation. The mean ED50s for the growth of leukemic blast progenitors were 1.6, 1.2, 0.7, and 0.2 pM in the presence of G-CSF, GM-CSF, IL-3, and SCF, respectively, c-myc and c-myb antisense oligonucleotides significantly suppressed the growth of leukemic blast progenitors, but not that of clonogenic cells from normal donors and patients with ET. We also demonstrated that TGF-beta 1 inhibits mRNA expression by AML blasts for c-myc and/or c-myb. When the data are taken together, growth suppression by TGF-beta 1 appears to increase with the progression of clonal evolution in hematologic malignancies.
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PMID:Differential effects of TGF-beta 1 on normal and leukemic human hematopoietic cell proliferation. 754 18

Deletions of chromosomal band 9p21 have been detected in various tumor types as well as in more than 20% of acute lymphoblastic leukemia (ALL). These deletions frequently include the entire interferon (IFN) gene cluster as well as the methylthioadenosine phosphorylase (MTAP) gene. Recently, the CDKN2 gene (p16INK4A, MTS I, CDK41) was proposed as a candidate tumor-suppressor gene on 9p21 because it is frequently deleted in cell lines derived from multiple tumor types. To determine if CDKN2 or another closely related gene on 9p is the target of 9p deletions in ALL and other hematologic malignancies, we analyzed 20 primary patient samples (13 ALL, 2 acute myeloid leukemias [AML], and 5 non-Hodgkin's lymphomas [NHL]) with 9p rearrangements using Southern blot analysis, fluorescence in situ hybridization (FISH), and single-strand conformation polymorphism (SSCP) for alterations of CDKN2. Homozygous deletions of the CDKN2/CDKN2B (p15) region were detected in 10 cases (50%; 6 ALL, 2 AML, and 2 NHL). In 1 additional case, the intensity of the Southern blot band was significantly reduced, suggesting a CDKN2 deletion in a subpopulation of the malignant cells. No CDKN2 or CDKN2B rearrangements were seen. The IFN gene cluster was homozygously deleted in 2 of 15 (13%) analyzed cases, whereas the MTAP gene was deleted in 6 of 15 cases (40%). In addition, hemizygous deletions of the CDKN2 region were identified in 6 ALL cases using interphase FISH. No point mutation of the coding region of CDKN2 was detected by SSCP in these cases. We conclude that CDKN2 is the most frequently homozygously deleted marker on 9p. The absence of point mutations in the coding region of CDKN2 in cases with hemizygous 9p deletions and the frequent codeletion of MTAP, CDKN2B, and other yet unidentified neighboring genes suggest that the simultaneous deletion of these genes may be necessary for the selective growth advantage of malignant cells.
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PMID:Refined mapping of genomic rearrangements involving the short arm of chromosome 9 in acute lymphoblastic leukemias and other hematologic malignancies. 754 47

Although activating mutations in ras genes are the most common genetic abnormality in human hematologic malignancies, the role of ras mutations as an initiating event in leukemogenesis remains unclear. To assess the consequences of ectopic expression of an activated ras gene in normal hematopoietic cells in vivo, lethally irradiated mice were reconstituted with bone marrow cells infected with a mutant ras-containing retrovirus [murine stem cell virus (MSCV)-v-H-ras] based on the MSCV retroviral vector which efficiently transduces functional genes into hematopoietic stem/progenitor cells. Despite a marked myeloid leukocytosis detectable in the peripheral blood within 4 weeks of engraftment, none of 22 primary or secondary transplant recipients studied for longer periods of time presented with myeloid neoplasms. Instead, 18 of the MSCV-v-H-ras mice developed pre-T-cell thymic lymphomas and/or pre-B-cell lymphoblastic leukemia/lymphomas between 7 and 12 weeks post-transplantation. The pre-B and pre-T lymphoid tumors that arose in one animal were shown to harbor a common MSCV-v-H-ras provirus, indicating that the target cell for transformation was a bipotential lymphoid precursor. To more precisely examine the effects of activated ras expression on the behavior of hematopoietic progenitors, infected bone marrow cells were assayed in methylcellulose cultures under conditions favorable for growth of multilineage myeloid colonies or were passaged as bulk suspension cultures in the presence of various hematopoietic growth factors, including interleukin (IL)-3, IL-4, IL-6 and IL-7. MSCV-directed expression of v-H-ras selectively promoted the formation of large dense colonies comprised of monocyte-macrophages in methylcellulose cultures. When transferred to liquid cultures, the vast majority of the cells underwent terminal macrophage differentiation. By comparison, tumorigenic B-lymphoid and mixed lymphoid/myeloid cell lines were routinely established from the bulk suspension cultures, with cell lines of predominantly myeloid phenotype emerging only in IL-6-supplemented cultures. These results, considered together with previous findings, suggest that activating ras mutations could be an initiating genetic alteration in human acute lymphoblastic leukemia but are more likely to be a post-initiation change in human acute myeloid leukemia.
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PMID:Hematopoietic transforming potential of activated ras in chimeric mice. 756 71

Microangiopathic disease and diffuse alveolar haemorrhage (DAH) are uncommon serious complications of bone marrow transplantation (BMT), but an association between these two conditions has not been previously recognised. We report 4 patients in whom these two complications occurred after allogeneic BMT for haematological malignancy. The patients were 16-39 years of age, and received transplants for acute myeloid leukemia, chronic myeloid leukemia and non-Hodgkin's lymphoma (n = 2). Donors were HLA-identical siblings (n = 3), and a matched unrelated volunteer. The patient with AML was receiving a second transplant for relapse 3 years after her first BMT, and was prepared with busulphan and melphalan; other patients received total body irradiation and cyclophosphamide. Microangiopathy occurred 20-48 days after BMT, and was associated with renal impairment in all cases, and mental confusion in 3. Cyclosporin levels were in the toxic range in 2 cases. DAH occurred 18-55 days after BMT, in 3 cases 2-7 days after the onset of microangiopathy, but preceding it by 14 days in the other case. Patients were treated with fresh frozen plasma, plasma exchange, supplemental oxygen and ventilation in 2 cases. Two patients died of progressive respiratory failure, while 2 patients recovered with evidence of continuing microangiopathic disease, and died of myocardial infarction or fungal infection. We report an association between microangiopathic disease and DAH in these BMT patients, and suggest that damage to the pulmonary vascular endothelium may be the common pathophysiological event, although no specific causative factor could be identified.
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PMID:Diffuse alveolar haemorrhage associated with microangiopathy after allogeneic bone marrow transplantation. 758 Oct 82

Comparative genomic hybridization (CGH) represents a new technique for global analysis of a whole genome for net loss or gain of chromosome regions. It offers several advantages over alternative techniques. It permits analysis of a whole genome in a single hybridization reaction, it does not require the generation of metaphases from tumor cells, and it only requires very small numbers of tumor cells. Most previous studies have concentrated on the application of CGH to the analysis of chromosome defects associated with solid tumors. In this paper we report the use of CGH to study bone marrow samples from a patient with acute myeloid leukemia and complex karyotypic abnormalities. The results obtained using CGH were compared with G-banding analysis. Both G-banding and CGH detected a 5q deletion, a 7q deletion, additional material derived from 8q, and an HSR on 11q. However, several apparently discrepant results were also obtained. Paints for chromosomes 3, 5, 7, 8, 11, 12, 14, 17, 22, and X were therefore used to resolve these differences. Our results demonstrate that CGH detected chromosome abnormalities associated with acute myeloid leukemia and that CGH provided information that was not obtained by G-banding analysis alone. These data suggest that CGH may prove a useful adjunct to conventional cytogenetic and molecular analysis of hematologic malignancies.
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PMID:Comparative genomic hybridization in acute myeloid leukemia. A comparison with G-banding and chromosome painting. 762 45

Unbalanced translocations as well as interstitial deletions of the short arm of chromosome 12 [del(12p)] are found as recurring chromosomal changes in a broad spectrum of hematopoietic malignancies. These changes result in the hemizygous deletion of genetic material from 12p. We mapped a yeast artificial chromosome containing the TEL gene, a cosmid contig containing part of TEL and a P1 contig containing the KIP1 gene to 12p13. These probes were used for fluorescence in situ hybridization to analyze samples from 47 patients with various hematologic malignancies who had unbalanced translocations (25 patients) leading to loss of 12p or deletions (22 patients) involving 12p13. The patients had acute lymphoblastic leukemia (8 cases), myelodysplastic syndrome (MDS; 11 cases), acute myeloid leukemia (AML; 10 cases), myeloproliferative disorders (4 cases), therapy-related MDS or AML (7 cases), non-Hodgkin's lymphoma (2 cases), and other hematopoietic malignancies (5 cases). All three probes were hemizygously detected in 26 cases and were completely retained in only 9 cases. In 12 cases probes for one of the two genes were deleted, allowing us to map the smallest region of overlap of these deletions to a small genomic region that is bordered on the telomeric side by the TEL gene and on the centromeric side by KIP1. The genomic distance between TEL and KIP1 is estimated to be about 1 to 2 Mbp.
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PMID:TEL and KIP1 define the smallest region of deletions on 12p13 in hematopoietic malignancies. 763 60


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