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

A 58-year-old man was referred to our hospital because of his refractory leukemia. Laboratory examinations showed mild anemia and leukocytosis but no blast was seen in the blood. The patient's bone marrow was hyperplastic and 64.8% of marrow cells were lymphoblastoid cells. They were positive for CD10, CD19, CD34 and HLA-DR antigen. Cytogenetic analysis revealed the Ph chromosome in 17 of 20 metaphases. A Southern blot analysis demonstrated no rearrangement of M-BCR gene. A diagnosis of Ph-positive ALL was made. The patient received chemotherapy and reached a complete remission. At that time, however, his marrow cells had Ph chromosome in 7 of 7 metaphases and rearrangement of m-BCR was positive in PCR analysis. He died of septic shock during the intensive consolidation therapy. Clinically this patient seems to have de novo Ph-positive ALL though his marrow cells had Ph chromosome in all metaphases at the time of complete remission. Recently the rare cases of Ph-positive CML with an m-BCR breakpoint are reported in the literature. This patient may have such a type of CML in blastic phase.
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PMID:[A patient with clinically de novo Ph-positive acute lymphoblastic leukemia had Ph chromosome in all metaphases at the time of hematological remission]. 891 71

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

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

Imatinib mesylate (IM) is a tyrosine kinase inhibitor, which inhibits phosphorylation of downstream proteins involved in BCR-ABL signal transduction. It has proved beneficial in treating patients with chronic myeloid leukaemia (CML). In addition, IM demonstrates activity against malignant cells expressing c-kit and platelet-derived growth factor receptor (PDGF-R). The activity of IM in the blastic crisis of CML and against various myeloma cell lines suggests that this drug may also target other cellular components. In the light of the important role of telomerase in malignant transformation, we evaluated the effect of IM on telomerase activity (TA) and regulation in various malignant cell lines. Imatinib mesylate caused a dose-dependent inhibition of TA (up to 90% at a concentration of 15 microM IM) in c-kit-expressing SK-N-MC (Ewing sarcoma), SK-MEL-28 (melanoma), RPMI 8226 (myeloma), MCF-7 (breast cancer) and HSC 536/N (Fanconi anaemia) cells as well as in ba/F3 (murine pro-B cells), which do not express c-kit, BCR-ABL or PDGF-R. Imatinib mesylate did not affect the activity of other DNA polymerases. Inhibition of TA was associated with 50% inhibition of proliferation. The inhibition of proliferation was associated with a decrease in the S-phase of the cell cycle and an accumulation of cells in the G2/M phase. No apoptosis was observed. Inhibition of TA was caused mainly by post-translational modifications: dephosphorylation of AKT and, to a smaller extent, by early downregulation of hTERT (the catalytic subunit of the enzyme) transcription. Other steps of telomerase regulation were not affected by IM. This study demonstrates an additional cellular target of IM, not necessarily mediated via known tyrosine kinases, that causes inhibition of TA and cell proliferation.
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PMID:Imatinib mesylate (Gleevec) downregulates telomerase activity and inhibits proliferation in telomerase-expressing cell lines. 1587 Jul 11


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