Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptin, a small protein encoded by chicken anemia virus (CAV) was expressed in various human hematologic malignant cell lines derived from leukemias and lymphoma. Three of these cell lines contain bcl-2 or BCR-ABL proteins, known to block apoptosis induced by chemotherapeutic compounds. By immunofluorescence and propidium-iodide staining apoptin was shown to induce apoptosis in all analysed cell lines. Early after expression, apoptin exhibited a fine-granular distribution in the still intact nucleus. Later, apoptin became aggregated and the nucleus segmented. The data with truncated apoptin indicate that for optimal induction of apoptosis apoptin has to be located in the nucleus.
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PMID:Apoptin, a protein encoded by chicken anemia virus, induces cell death in various human hematologic malignant cells in vitro. 747 2

A 70-year-old male was admitted because of anemia in September 1989, and primary myelofibrosis was diagnosed based on the presence of leukoerythroblastosis, a normal chromosomal analysis and pathological findings of fibrosis in bone marrow. Although he was anemic, he did not require any treatment for two years. Then his hematological status deteriorated to severe pancytopenia, and the marrow biopsy revealed marked hypoplasia with fatty replacement and scattered fibrosis. He was treated with metenolon without success and frequent transfusion of packed red cell was required. This hypoplastic status continued for seven months. In May 1992 his WBC count increased gradually with monocytosis. The marrow was filled with various stages of monocytes, with almost no fibrosis remaining. The chromosomal analysis was repeated but disclosed no abnormalities, consistent with the negative result of BCR-ABL rearrangement investigated by the RT-PCR method. One month later, when the patient died of multiple cerebral bleeding and infection, the leukocyte count exceed 90,000/microliters. It is known that major causes of death for patients with primary myelofibrosis are infection, bleeding, cardiac trouble and transformation to leukemia. We describe a case of myelofibrosis who developed to chronic myelomonocytic leukemia following severe aplastic phase.
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PMID:[Transformation into chronic myelomonocytic leukemia in a patient with primary myelofibrosis associated with severe hypoplasia: report of an autopsy case]. 778 40

We describe a patient with Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukaemia (ALL) who developed it 2.5 years after being diagnosed with myelodysplastic syndrome (MDS). The patient initially had refractory anaemia (RA), but progressed to refractory anaemia with excess blasts (RAEB) 2 years later, that terminated in ALL. An immunophenotypic analysis of the lymphoblasts revealed CD10 and CD19 positive cells. The karyotype was normal 46,XY in RA phase, 46,XY,20q-during the RAEB phase, and 46,XY,t(9;22)(q34;q11),20q-during the ALL phase. Furthermore, p190 BCR-ABL mRNA was detected in the ALL blasts. These findings indicate that this ALL arose from the MDS clone through multiple cytogenetic evolutions, the final event of which was the acquisition of p190 BCR-ABL type Ph1.
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PMID:Progression from myelodysplastic syndrome to acute lymphoblastic leukaemia with Philadelphia chromosome and p190 BCR-ABL transcript. 863 33

Patients with chronic myeloid leukemia (CML) show the Philadelphia (Ph) translocation in more than 95% of the cases. The remaining cases, without the cytogenetic or molecular equivalent of the BCR-ABL rearrangement, are "Philadelphia negative" and may have alternate chromosomal aberrations. Ph negative CML patients are known to have a poor prognosis. We report on a young patient with a hypereosinophilic syndrome in the presence of a clonal translocation t(4;7) with a peripheral leukocytosis, a severe thrombocytopenia, and anemia at first presentation, who developed bone marrow changes typical of CML. Bone marrow function and hypereosinophilia improved only partially and temporarily under therapy. The patient died 10 months after diagnosis of diffuse leukemic embolism and organ infiltration resulting in paraplegia. The case demonstrates that beside "idiopathic" hypereosinophilic syndromes (HES), a proportion of such patients suffer from eosinophilic leukemias. In these cases, karyotype analysis may help to distinguish these states by the identification of clonal chromosomal abnormalities. A karyotype anomaly hitherto not reported can be added to the list of aberrations in hypereosinophilic states associated with myeloproliferative processes.
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PMID:Chronic myeloid leukemia associated hypereosinophilic syndrome with a clonal t(4;7)(q11;q32). 910 34

An immunosuppressive but not myeloablative regimen followed by HLA-matched donor mobilized haemopoietic stem cell transplantation was employed in two high-risk patients. The first patient had refractory anaemia with excess blasts (RAEB) and cytogenetic evidence of translocation 1;3(p36;q21). The second patient had Philadelphia-negative but p190 BCR-ABL chimaeric gene positive chronic myelogenous leukaemia in accelerated phase (AP-CML). The conditioning regimen consisted of fludarabine (30 mg/m2/d, days 1-3) with cyclophosphamide (300 mg/m2/d, days 1-3). Cyclosporine and methotrexate were employed for acute graft-versus-host disease (aGVHD) prophylaxis. In both cases the engraftment of donor cells was demonstrated by cytogenetics and short tandem repeat polymorphisms via PCR. Both patients are alive with normal cytogenetic (RAEB) and molecular (AP-CML) remissions, 100 and 150 d after allografting, respectively. In particular, in the AP-CML patient, the BCR-ABL became undetectable and the BCR-ABL/ABL ratio was <0.0001.
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PMID:Evidence of cytogenetic and molecular remission by allogeneic cells after immunosuppressive therapy alone. 982 37

Erythropoietin (Epo)-independent differentiation of erythroid progenitors is a major characteristic of myeloproliferative disorders, including chronic myeloid leukemia. Epo receptor (EpoR) signaling is crucial for normal erythroid development, as evidenced by the properties of Epo(-/-) and EpoR(-/-) mice, which contain a normal number of fetal liver erythroid progenitors but die in utero from a severe anemia attributable to the absence of red cell maturation. Here we show that two constitutively active cytoplasmic protein tyrosine kinases, P210(BCR-ABL) and v-SRC, can functionally replace the EpoR and support full proliferation, differentiation, and maturation of fetal liver erythroid progenitors from EpoR(-/-) mice. These protein tyrosine kinases can also partially complement the myeloid growth factors IL-3, IL-6, and Steel factor, which are normally required in addition to Epo for erythroid development. Additionally, BCR-ABL mutants that lack residues necessary for transformation of fibroblasts or bone marrow cells can fully support normal erythroid development. These results demonstrate that activated tyrosine kinase oncoproteins implicated in tumorigenesis and human leukemia can functionally complement for cytokine receptor signaling pathways to support normal erythropoiesis in EpoR-deficient cells. Moreover, terminal differentiation of erythroid cells requires generic signals provided by activated protein tyrosine kinases and does not require a specific signal unique to a cytokine receptor.
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PMID:BCR-ABL and v-SRC tyrosine kinase oncoproteins support normal erythroid development in erythropoietin receptor-deficient progenitor cells. 1055 95

This report presents two rare cases, one of paediatric myelodysplastic syndrome (MDS) and the other juvenile chronic myeloid leukaemia (jCML). In the first case, there were clinical and biological features of MDS-refractory anaemia with excess blasts (RAEB). The bone marrow (BM) karyotype demonstrated a monosomy 7 which was confirmed by fluorescence in situ hybridization (FISH). In addition, FISH analysis showed that an alpha-satellite DNA sequence had been transferred from chromosomes 13/21 to one homologue of chromosomes 22. The BCR-ABL rearrangement was negative. In the second case, at diagnosis, the karyotype was 46,XX. FISH analysis with the simultaneous and individual application of abl and bcr probes for chromosome 9 and 22, respectively, revealed the presence of the BCR-ABL rearrangement in addition to an extra ABL sequence locating chromosome 20. A clone that was BCR-ABL gene rearrangement negative but with an extra ABL DNA sequence on chromsome 20, and another clone that was BCR-ABL gene rearrangement negative were detected by DC-FISH and uni-colour (UC-) FISH analysis. No monosomy 7 was detected by conventional cytogenetic or FISH analyses.
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PMID:Paediatric myelodysplastic syndrome (MDS) and juvenile chronic myelogenous leukaemia (JCML) detected by cytogenetic and FISH techniques. 1067 94

BCR/ABL, the oncoprotein responsible for chronic myeloid leukemia (CML), transforms hematopoietic cells through both Ras-dependent and -independent mechanisms. Farnesyl protein transferase inhibitors (FTIs) were designed to block mutant Ras signaling, but they also inhibit the growth of transformed cells with wild-type Ras, implying that other farnesylated targets contribute to FTI action. In the current study, the clinical candidate FTI SCH66336 was characterized for its ability to inhibit BCR/ABL transformation. When tested against BCR/ABL-BaF3 cells, a murine cell line that is leukemogenic in mice, SCH66336 potently inhibited soft agar colony formation, slowed proliferation, and sensitized cells to apoptotic stimuli. Quantification of activated guanosine triphosphate (GTP)-bound Ras protein and electrophoretic mobility shift assays for AP-1 DNA binding showed that Ras effector pathways are inhibited by SCH66336. However, SCH66336 was more inhibitory than dominant-negative Ras in assays of soft agar colony formation and cell proliferation, suggesting activity against targets other than Ras. Cell cycle analysis of BCR/ABL-BaF3 cells treated with SCH66336 revealed G2/M blockade, consistent with recent reports that centromeric proteins that regulate the G2/M checkpoint are critical farnesylated targets of FTI action. Mice injected intravenously with BCR/ABL-BaF3 cells developed acute leukemia and died within 4 weeks with massive splenomegaly, elevated white blood cell counts, and anemia. In contrast, nearly all mice treated with SCH66336 survived and have remained disease-free for more than a year. Furthermore, SCH66336 selectively inhibited the hematopoietic colony formation of primary human CML cells. As an oral, nontoxic compound with a mechanism of action distinct from that of ABL tyrosine kinase inhibition, FTI SCH66336 shows promise for the treatment of BCR/ABL-induced leukemia.
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PMID:Activity of the farnesyl protein transferase inhibitor SCH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia. 1122 87

Myeloid neoplasia has been studied extensively in human beings but has not been reported in macaques. A 2-year-old female rhesus macaque that was experimentally exposed to lead as a neonate, was noted to have immature circulating myelocytic cells, including 1% blasts, and normocytic normochromic anemia on a blood sample obtained for monthly health monitoring. The animal was treated with hydroxyurea, blood transfusion, and recombinant human erythropoietin to reduce the leukocytosis and correct the anemia. The disease had a relatively indolent course for 3 months, when it progressed to blast crisis. After the onset of blast crisis, the animal was euthanized because of bleeding problems, anemia, and a progressive decline in her health. The animal was negative by serology, polymerase chain reaction (PCR) assays, and/or culture for simian retrovirus (SRV), simian T-lymphotropic virus type I (STLV-I), and simian immunodeficiency virus (SIV). PCR assay for the bcr-ABL chromosomal translocation using primers made for the human gene was negative. Serology for Epstein-Barr virus (EBV)-like viruses was positive for IgG directed against the viral nucleocapsid antigen, but epidemiologic factors make it unlikely that the leukemia was associated with EBV-induced viral transformation. Lead exposure has been associated with neoplasia in human beings, and the possible role of neonatal lead exposure in hematologic neoplasias deserves further scrutiny.
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PMID:Chronic myelocytic leukemia in a juvenile rhesus macaque (Macaca mulatta). 1145 96

The receptor-associated protein tyrosine kinase janus-kinase 2 (JAK2) is essential for normal red cell development and for erythropoietin receptor (EpoR) signaling. JAK2(-/-) embryos are severely deficient in erythropoiesis and die at an early stage of development from fetal anemia. The binding of erythropoietin (Epo) to the EpoR triggers the activation of JAK2, the phosphorylation of the EpoR, and the initiation of the EpoR signaling cascade. In addition to Epo binding to its receptor, signaling pathways downstream of the EpoR can also be stimulated by the BCR-ABL oncoprotein. This study explored whether JAK2 is required for BCR-ABL-mediated stimulation of erythropoiesis. Here, it is shown that JAK2 is constitutively tyrosine phosphorylated in cultured and primary erythroid cells expressing BCR-ABL. However, BCR-ABL effectively supports normal erythroid proliferation, differentiation, and maturation in JAK2-deficient fetal liver cells. Using mutants of BCR-ABL, this study shows that certain signaling pathways activated by BCR-ABL segments distinct from its tyrosine kinase domain are essential for rescue of erythropoiesis in JAK2(-/-) progenitors. The consequences of these multiple signaling pathways for normal erythroid development are discussed.
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PMID:Erythropoiesis in the absence of janus-kinase 2: BCR-ABL induces red cell formation in JAK2(-/-) hematopoietic progenitors. 1169 76


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