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

A 41-year-old man visited his doctor in May 2000 because of a sore throat and high fever. His symptoms did not improve, despite administration of antibiotics and nonsteroidal anti-inflammatory drugs. Since a chest X-ray examination revealed an anterior mediastinal bulky tumor, he was referred and admitted to our hospital on June 21, 2000. The peripheral white blood cell count was 44,540/microliter with 74% myeloblasts. Bone marrow aspiration revealed a hypercellular marrow with 82% myeloblasts, which were negative for peroxidase and alpha-naphthyl butylate esterase staining. Blast cells were positive for CD7, CD13, CD33, CD34, and HLA-DR, and negative for CD56. A needle biopsy specimen of the mediastinal tumor consisted of myeloblasts. We diagnosed the patient as having CD7 (+) acute myeloid leukemia (AML) (M0) with a bulky mediastinal mass based on the surface marker analysis, although the clinical features resembled myeloid/NK precursor acute leukemia. The patient achieved a complete remission after two courses of induction therapy. We are planning an allogeneic stem cell transplantation during his first remission because of the high risk of relapse.
 ...
PMID:[CD7(+) acute myeloid leukemia (M0) associated with a mediastinal bulky mass lesion]. 1157 5

Interstitial deletion or loss of chromosome 5, del(5q) or -5, is a frequent finding in myeloid leukemias and myelodysplasias, suggesting the presence of a tumor suppressor gene within the deleted region. In our search for this gene, we identified a candidate, 5qNCA (LOC51780), which lies within a consistently-deleted segment of 5q31. 5qNCA expresses a 7.2-kb transcript with a 5286-bp open reading frame which is present at high levels in heart, skeletal muscle, kidney, placenta, and liver as well as CD34+ cells and AML cell lines. 5qNCA encodes a 191-kD nuclear protein which contains a highly-conserved C-terminus containing a zinc finger with the unique spacing Cys-X2-Cys-X7-His-X2-Cys-X2-Cys-X4-Cys-X2-Cys and a jmjC domain, which is often found in proteins that regulate chromatin remodeling. Expression of 5qNCA in a del(5q) cell line results in suppression of clonogenic growth. Preliminary sequence results in AML and MDS samples and cell lines has revealed a possible mutation in the KG-1 cell line resulting in a THR to ALA substitution that has not been found in over 100 normal alleles to date. We propose 5qNCA is a good candidate for the del(5q) tumor suppressor gene based on its predicted function and growth suppressive activities, and suggest that further mutational and functional study of this interesting gene is warranted.
 ...
PMID:A novel nuclear protein, 5qNCA (LOC51780) is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31. 1168 74

Through the hard work of a large number of investigators, the biology of acute myeloid leukemia (AML) is becoming increasingly well understood, and as a consequence, new therapeutic targets have been identified and new model systems have been developed for testing novel therapies. How these new therapies can be most effectively studied in the clinic and whether they will ultimately improve cure rates are questions of enormous importance. In this article, Dr. Jacob Rowe presents a summary of the current state-of-the-art therapy for adult AML. His contribution emphasizes the fact that AML is not a single disease, but a number of related diseases each distinguished by unique cytogenetic markers which in turn help determine the most appropriate treatment. Dr. Jerald Radich continues on this theme, emphasizing how these cytogenetic abnormalities, as well as other mutations, give rise to abnormal signal transduction and how these abnormal pathways may represent ideal targets for the development of new therapeutics. A third contribution by Dr. Frederick Appelbaum describes how AML might be made the target of immunologic attack. Specifically, strategies using antibody-based or cell-based immunotherapies are described including the use of unmodified antibodies, drug conjugates, radioimmunoconjugates, non-ablative allogeneic transplantation, T cell adoptive immunotherapy and AML vaccines. Finally, Dr. John Dick provides a review of the development of the NOD/SCID mouse model of human AML emphasizing both what it has taught us about the biology of the disease as well as how it can be used to test new therapies. Taken together, these reviews are meant to help us understand more about where we are in the treatment of AML, where we can go and how we might get there.
 ...
PMID:Acute myeloid leukemia. 1172 79

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, APO2L) has been shown to induce apoptosis in a number of tumor cell lines as well as in some primary tumors whereas cells from most normal tissues are highly resistant to TRAIL-induced apoptosis. We have studied the susceptibility of primary malignant and normal bone marrow hematopoietic progenitors to TRAIL-induced apoptosis. Extracellular domain of human TRAIL with N-terminal His(6) tag (His-TRAIL, amino acids 95-281) was produced in E. coli and its apoptosis-inducing ability was compared with the leucine-zipper containing TRAIL, LZ-TRAIL. Both variants of TRAIL had the same apoptosis-inducing ability. Clonogenic progenitor assays showed that His-TRAIL significantly reduced the number of myeloid colonies (CFU-GM) and clusters from patients with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndromes (MDS). His-TRAIL had no negative effect on the number of CFU-GM colonies and clusters derived from bone marrow cells of AML patients in complete remission, and lymphoma patients without bone marrow involvement, as well as those derived from normal cord blood cells. Moreover, we found that normal human stem cells treated with high doses of His-TRAIL maintain a repopulating potential when transplanted into NOD/SCID mice. To conclude, our data document that TRAIL does not affect normal human hematopoiesis but suppresses the growth of early primary leukemia and myelodysplasia progenitors.
 ...
PMID:TRAIL (Apo2L) suppresses growth of primary human leukemia and myelodysplasia progenitors. 1184 Feb 65

The patient was a 62-year-old man. His hematological data in April 2000 had shown no abnormalities, but he was referred to our hospital because of a fever and leukocytosis in June 2000. The peripheral blood showed 29.8 x 10(9)/L white blood cells, with 68.0% blasts. A bone marrow aspirate showed hypercellularity with a proliferation of large leukemic blasts. The leukemic cells were positive for CD13 (91%), CD33 (54.8%), CD34 (94.5%), and HLA-DR (97.9%). Some leukemic cells (15.6%) also expressed CD14. Cytogenetic analysis revealed 92,XXYY,t(9;22)(q34;q11)x2 in all 20 metaphase cells. Reverse transcriptase polymerase chain reaction analysis detected the minor BCR/ABL messenger RNA (mRNA) but failed to detect the major BCR/ABL mRNA. The patient achieved complete remission after induction chemotherapy, with no evidence of Philadelphia chromosome (Ph) or minor BCR/ABL mRNA. Ph-positive acute myeloid leukemia (Ph-AML) has rarely been reported. Herein, we report a case of Ph-AML with tetraploidy and review the previously reported Ph-AML cases.
 ...
PMID:Philadelphia chromosome-positive acute myeloid leukemia with tetraploidy. 1184 93

The beginning of this century was marked, in our specialty as in other, by two revolutions: the routine use of molecular biology tools for a better prognosis of the disease (flt3 receptor duplication in AML, mutational profile of Ig genes in CLL, gene expression profile with ARN chips in aggressive lymphomas.), and the discovery of "intelligent" molecules, targeting the tumoral cell. In this category, the most appealing is the STI571 (Gleevec , Novartis), targeting the molecular abnormality of the cells expressing bcr-abl protein: CML, ALL Ph1(+). Other molecules targeting signal transduction proteins (ras farnesylation inhibitors for example) are already in clinical trials. The increasing therapeutic use of monoclonal antibodies is also to be cited, with a special mention concerning the rituximab, used in several B lymphoid pathologies, from lymphoma to autoimmune diseases. His very good tolerance permits his use in ambulatory patients, and his combination with chemotherapy or his linkage with radioactive elements render this molecule indispensable. The other side of these molecules is their incredibly high cost, explaining the uncontrolled expenses in 2001 of hospitals hosting hematology as well as oncology activities.
 ...
PMID:[Update on malignant hemopathies]. 1184 29

Acute myeloid leukaemia (AML) cases with different chromosomal abnormalities may reflect different aetiologies. Benzene exposure, from a number of sources including smoking, is one risk factor for AML. Individual susceptibility to benzene may depend on differences in expression of metabolizing enzymes. We tested the hypothesis that smoking as well as genetic polymorphisms in the microsomal epoxide hydrolase gene (HYL1), an enzyme involved in benzene metabolism, could be risk factors for AML with defined chromosomal abnormalities. Twenty-six AML cases with -7/del(7q) and 24 cases with t(8;21), as well as 43 cases with normal karyotype and 155 age-, sex- and residence-matched controls, were drawn from a large case-control study on adult acute leukaemia. Current smoking was significantly associated with the cytogenetic abnormalities t(8;21) or -7/del(7q) (OR = 4.9; 95%CI = 2.1-11.5) but not with a normal karyotype, relative to individuals who were not current smokers. A putative high activity HYL1 phenotype [exon 3, residue 113 (Tyr/Tyr) and exon 4, residue 139 (His/Arg or Arg/Arg)] was associated with a significantly increased AML risk in men with -7/del(7q) or t(8;21) (OR = 4.4; 95%CI 1.1-17.0) but not with a normal karyotype. This suggests that AML cases with defined chromosomal abnormalities could be related to specific carcinogen exposures and, furthermore, suggests that smoking and genetic polymorphisms in HYL1 could be risk factors for AML with -7/del(7q) or t(8;21).
 ...
PMID:Genetic polymorphisms in microsomal epoxide hydrolase and susceptibility to adult acute myeloid leukaemia with defined cytogenetic abnormalities. 1184 15

46-year-old patient with acute myeloid leukemia (AML) whose disease manifested as fever, chills and dry cough is reported here. Despite broad antibiotic coverage he remained acutely ill with spiking fever, shaking chills, and hypoxemia. His initial chest radiograph was normal but chest computed tomography (CT) scan disclosed bilateral focal infiltrates. Hypoxemia and severe thrombocytopenia precluded invasive diagnostic procedures. A thorough epidemiological investigation revealed that before becoming acutely ill the patient smoked daily tobacco mixed with marijuana from a "hookah bottle". While waiting for tobacco and "hookah water" cultures, we started antifungal therapy. Resolution of fever and hypoxemia ensued after 72 hours. Tobacco cultures yielded heavy growth of Aspergillus species. We suggest that habitual smoking of Aspergillus-infested tobacco and marijuana caused airway colonization with Aspergillus. Leukemia rendered the patient immunocompromised, and allowed Aspergillus to infest the lung parenchyma with early occurrence of invasive pulmonary aspergillosis. Physicians should be aware of this potentially lethal complication of "hookah" and marijuana smoking in immunocompromised hosts.
 ...
PMID:Early invasive pulmonary aspergillosis in a leukemia patient linked to aspergillus contaminated marijuana smoking. 1191 32

We describe a 69-year-old Japanese male with acute leukemia with a CD7+ and CD56+ immunophenotype presenting with multiple lymphadenopathy. He was treated with idarubicin and cytosine arabinoside. Although the leukemia showed partial response, the patient did not achieve complete remission. He died of sepsis due to severe neutropenia after the third course of chemotherapy. His autopsy revealed blast infiltration in the lymph nodes, liver, spleen and vertebral bone marrow. Recently, CD7+ and CD56+ myeloid/natural killer precursor acute leukemia has been associated with a poor prognosis. Our case illustrates that myeloid/natural killer cell precursor acute leukemia shows some response to intensive chemotherapy for acute myeloid leukemia, but such therapy is insufficient to effect a cure. To overcome the resistance of this disease to chemotherapy, further studies should explore other treatment strategies.
 ...
PMID:CD7+ and CD56+ myeloid/natural killer cell precursor acute leukemia treated with idarubicin and cytosine arabinoside. 1214 68

ETV6, a member of the Ets family of transcription factors, is frequently rearranged to various translocation partners in human leukaemias. We previously described a CD3+/TCRalpha/beta+ mature T-cell acute lymphoblastic leukaemia (T-ALL) cell line, MT-ALL, carrying a t(1;10;12)(q25; p13;p13) with cytokine-inducible lineage switch into the myeloid lineage. Using reverse transcription polymerase chain reaction with primers complementary to ETV6 and ABL2, two ETV6-ABL2 fusion transcripts were identified in MT-ALL which resulted from alternative splicing of an ABL2 exon. The fusion transcripts code for putative ETV6-ABL2 fusion proteins containing the pointed domain of ETV6 and almost the complete ABL2 protein, including the SH2, SH3 domains and the protein tyrosine kinase domain (PTK). Identical ETV6-ABL2 fusion transcripts have been reported in an acute myeloid leukaemia (AML) M3 cell line, carrying both a t(15;17)(q22;q21) and a t(1;12)(q25;p13) with unusual inducible differentiation to eosinophils, and in a patient with AML-M4eo. Interestingly, the non-rearranged allele of ETV6 in the MT-ALL cell line carries an arginine to histidine (R399H) mutation which affects a conserved amino acid in the ets DNA binding domain.
 ...
PMID:Identification of an ETV6-ABL2 fusion transcript in combination with an ETV6 point mutation in a T-cell acute lymphoblastic leukaemia cell line. 1240 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>