Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A genomic fragment containing the 5' boundary of the von Willebrand factor pseudogene was cloned, partially sequenced and used for in situ hybridization experiments on metaphase spreads from a Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia patient. Data obtained indicate that the von Willebrand factor pseudogenic region is centromeric to the breakpoint cluster region on 22q11.2. This probe could be used for the study of deletions in the DiGeorge syndrome.
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PMID:Characterization and mapping of the 5' portion of von Willebrand factor pseudogene. 148 45

Glycoprotein Ib (GPIb), the receptor for von Willebrand factor, is a two-chain member constituent of the platelet/megakaryocytic lineage. Studies on its expression have been hampered by the difficulties in obtaining purified megakaryocytes in a sufficient number. We report a suspension liquid culture procedure that allowed isolation of more than 1 x 10(6) megakaryocytes with a purity ranging from 3% to 88% from the blood of patients with chronic myeloid leukemia, from fetal liver or from normal human bone marrow. GPIb was detected on the plasma membrane of all maturing megakaryocytes and also of promegakaryoblasts devoid of demarcation membranes. GPIb was detected on demarcation membranes of maturing megakaryocytes but was absent from all other organelles, including alpha granules. Biosynthesis of 35S-methionine labeled megakaryocytes showed that GPIb with similar electrophoretic mobility to the platelet molecule was synthesized and that it was also composed of two chains, since its molecular weight shifted in reducing conditions from 170 Kd to 145 Kd. The beta chain remained undetectable after methionine metabolic labeling, but it was immunoprecipitated after 3H-leucine metabolic labeling, confirming that this subunit is devoid of methionine. GPIb was associated with GPIX, as it is in platelets, since anti-GPIb antibodies coprecipitated a 17 Kd polypeptide.
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PMID:Expression of platelet glycoprotein Ib by cultured human megakaryocytes: ultrastructural localization and biosynthesis. 219 92

Three cases of megakaryoblastic transformation of chronic granulocytic leukemia (CGL) are reported. In each case, the leukemic transformation had morphologic features suggesting megakaryocytic differentiation. This was confirmed by positive immunostaining with a monoclonal antibody (HP1-1D) specific for platelet and megakaryocyte glycoprotein IIb/IIIa antigen, which was expressed by the majority of the leukemic blasts in all three cases. Cases with evidence of multilineage differentiation of the leukemic transformation were excluded. A striking feature in two patients was the manifestation of lytic bone lesions and soft tissue masses at presentation. A biopsy of a lytic bone lesion and soft tissue mass in one patient revealed a megakaryoblastic leukemic infiltrate, which by immunocytochemical staining was positive for the megakaryocytic markers, glycoprotein IIb/IIIa antigen, and Factor VIII (von Willebrand factor) antigen. In contrast to granulocytic sarcomas, the megakaryoblastic sarcoma did not stain cytochemically for chloroacetate esterase. The mean survival after acute transformation was 5.3 months. The three cases of megakaryoblastic transformation represented a significant proportion of all CGL blastic transformation cases (ten cases) evaluated by bone marrow examination in our institution during a 13-month period. Megakaryoblastic transformation of CGL may occur more frequently than has been appreciated, and can present as lytic bone lesions or as soft tissue megakaryoblastic sarcomas.
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PMID:Megakaryoblastic transformation of chronic granulocytic leukemia. 243 83

The receptor on human neutrophils (polymorphonuclear leukocytes) that mediates cellular adherence consists of two noncovalently associated subunits, designated alpha M (Mac-1 alpha, Mol alpha, or CD11b; Mr, 170,000) and beta (Mac-1 beta, Mol beta, or CD18; Mr, 100,000). We isolated a cDNA clone for the human neutrophil alpha M subunit by screening a lambda gt 11 cDNA library made from chronic myelogenous leukemia neutrophils by using an affinity-purified rabbit polyclonal antibody directed against the alpha M subunit. We used this cDNA clone to obtain additional clones from cDNA libraries made from differentiated HL-60 promyelocytic leukemia cells. Together these cDNAs constitute the complete 1137-amino acid sequence for the mature human alpha M subunit protein. The deduced amino acid sequence indicates the presence of an extensive extracellular domain with three putative metal-binding regions, (i) an amino acid region that is homologous to the A domain of von Willebrand factor, (ii) a 26-amino acid hydrophobic sequence that is a potential transmembrane domain, and (iii) a 19-amino acid cytoplasmic region. The amino acid sequence for the human neutrophil alpha M subunit contains regions that are closely related to amino acid sequences of adhesion receptors belonging to the integrin family.
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PMID:cDNA sequence for the alpha M subunit of the human neutrophil adherence receptor indicates homology to integrin alpha subunits. 256 62

The number and functional activity of membrane glycoproteins (GP) Ib and IIb/IIIa were investigated in platelets from 11 patients with myeloproliferative disorders (MPD). Three patients had essential thrombocythaemia, two had chronic myeloid leukaemia and six had polycythaemia vera. The numbers of GPIb and GPIIb/IIIa molecules were detected on the platelet surface using different 125I-labelled monoclonal antibodies. The functional properties of GPIb and GPIIb/IIIa were evaluated using purified 125I-labelled asialo von Willebrand factor (vWF) and purified 125I-labelled fibrinogen, respectively, in a binding assay. Binding of the anti-GPIIb/IIIa antibody was decreased by 40% in almost all patients studied and, when measured, it was accompanied by decreased fibrinogen binding to activated platelets. Binding of anti-GPIb antibodies to platelets was also slightly decreased or virtually the same in eight out of 11 patients. The decrease correlated with decreased binding of asialo vWF. The increased plasma glycocalicin levels, measured in four patients, depended on the high platelet count. Scatchard analysis revealed normal receptor binding affinity for all ligands tested in all but one patient. In this report we demonstrate that abnormalities in the concentrations of GPIIb/IIIa membrane proteins are commonly present in patients with MPD, while a decrease in GPIb concentration is also seen, although in fewer patients. These abnormalities are accompanied by a concurrent decrease in the respective receptor functions. These findings may explain part of the haemorrhagic tendency often encountered in MPD.
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PMID:Platelet membrane abnormalities in myeloproliferative disorders: decrease in glycoproteins Ib and IIb/IIIa complex is associated with deficient receptor function. 260 23

Diagnostic significance of the megakaryocyte markers and clinical findings were evaluated in three cases with chronic myelogenous leukemia in megakaryoblastic crisis. Platelet peroxidase (PPO), glycoprotein IIb/IIIa, Ib, von Willebrand factor antigen (vWF: Ag) and demarcation membrane system (DMS) were examined as the megakaryocyte markers. Blast phenotypes were as follows: PPO- IIb/IIIa+ vWF: Ag+ DMS+ in Case 1, PPO+ IIb/IIIa +/- Ib- vWF: Ag +/- in Case 2 and PPO+ IIb/IIIa+ vWF: Ag +/- DMS +/- in Case 3 (-: 0% +/-: less than 10% +: greater than or equal to 10%). In Cases 1 and 3, no markers other than those for the megakaryocyte lineage were detected, but myeloperoxidase-positive blasts coexisted with PPO-positive megakaryoblasts in Case 2. Megakaryoblast phenotypes and involvement of other lineages were much different in each case. Therefore, marker study for cytological diagnosis should be performed in consideration of lineage heterogeneity. As to the clinical findings, no clear features common to the three cases were present. However, multiple osteolytic lesions were demonstrated on bone survey in Case 1 and considered to be caused by the proliferation of megakaryoblasts.
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PMID:[Megakaryoblastic crisis of chronic myelogenous leukemia cytological and clinical studies in three cases]. 279 2

Splenectomy performed in a patient with polycythaemia vera and incipient osteomyelofibrosis was complicated by severe postoperative bleeding. A transient decrease of factor VIII/von Willebrand factor (VIIIR:WF) was detected as a possible cause of the bleeding tendency. As a result of this observation the VIIIR:WF system was investigated in all patients with myeloproliferative disorders who are presently followed by this laboratory. Subnormal VIIIR:WF activity was found in 5 of 9 prospectively investigated patients with polycythaemia vera and in one of 12 patients with chronic myeloid leukemia. These results suggest that acquired defects of the VIIIR:WF system are, in addition to the well known functional abnormalities of blood platelets, quite common in myeloproliferative disorders, especially polycythaemia vera, and must be reckoned with before surgery in particular. When specific antibodies directed against VIIIR:WF have been ruled out, the etiology of the VIIIR:WF defect found in our patients remains unclear.
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PMID:[Hemostasis disorders with reduced activity of the von Willebrand factor in myeloproliferative syndromes]. 660 16

Plasma and platelet von Willebrand factor (vWF) measurements, multimeric pattern and subunit composition of plasma vWF were obtained in 29 consecutive patients with chronic myeloproliferative syndromes. In the 8 patients with chronic myelogenous leukemia (CML), plasma vWF was significantly higher than in the 11 patients with essential thrombocythemia (ET) and in the 10 patients with polycythemia vera (PV). The RiCof/vWF:Ag ratio was low in all these groups of patients (mean 0.64 +/- 0.1, 0.66 +/- 0.2, and 0.61 +/- 0.2; normal 0.97 +/- 0.2). Bleeding time was prolonged (> 7.5 min) in 1/8 CML patients, 1/10 with PV, and 3/11 with ET. Plasma vWF multimers showed a minor loss of the largest multimers in 3/8 patients with CML, 4/10 with PV, and a more severe reduction in 9/11 ET patients. The latter pattern correlated with an abnormal proteolysis of vWF, expressed by a major increase of the 140-Kd fragment and decrease of the intact 225-Kd subunit in ET patients, whereas the 176-Kd fragment was significantly increased in all the subgroups of patients. Platelet vWF was significantly higher in CML patients in comparison to ET and normal controls. However, minor losses of the larger multimers were evident in all the subsets of patients. In ET patients also the intermediate forms were lacking in platelets, accompanied by a significant decrease of platelet RiCof. This abnormality was significantly correlated with the occurrence of bleeding symptoms in PV and ET patients (P = 0.007; Fisher's exact test). In conclusion, plasma and platelet vWF abnormalities are common findings in myeloproliferative syndromes and are more severe in ET. The more pronounced platelet vWF abnormalities in ET may reflect the more frequent bleeding symptoms observed in this disorder.
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PMID:Platelet von Willebrand factor abnormalities in myeloproliferative syndromes. 763 73

The role of mixed hematopoietic chimerism in engraftment and relapse after allogeneic BMT remains unclear. To better evaluate post-transplant chimerism we used polymerase chain reaction (PCR) in vitro amplification of four single locus simple repetitive DNA sequences, all of which vary extensively in their repeat number among different individuals: variable number of tandem repeats D1S80, APOB and D17S5, and the tetranucleotide repeat F8VWF. We tested 13 cases of CML, four of multiple myeloma (MM), three of ANLL and one of B-CLL. In a sequential analysis protocol with the different loci, the donor could be distinguished from the recipient in 14 of 20 (70%) pairs with the first marker used (D1S80). When a donor of opposite sex was involved, karyotyping and Y chromosome-specific PCR were also used. With the use of the four markers, chimerism was identified in all the pairs. Mixed chimerism was present in 5 patients, and complete chimerism in 15. No patients relapsed. The application of PCR for documenting post-transplant chimerism has several advantages over Southern blotting: increased sensitivity, use of small amounts of sample, ease of preparation of DNA, elimination of restriction enzyme analysis and of radioisotopes, and speed.
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PMID:In vitro amplification of hypervariable DNA regions for the evaluation of chimerism after allogeneic BMT. 840 55

Six patients with thrombotic microangiopathy associated with drug therapy had serial analyses of von Willebrand factor (vWF) multimeric patterns in their EDTA-plasma samples by sodium dodecyl sulfate-1% agarose gel electrophoresis and autoradiography. In the plasma of five patients (one with chronic myelogenous leukemia, two with prostatic cancer, and two with lymphoma), vWF abnormalities were observed during evolution of the thrombotic microangiopathy. These abnormalities were either the presence of unusually large (UL)vWF multimers of the type similar to those found within, and released or secreted by, endothelial cells (three patients) or a relative decrease in the largest plasma vWF multimers of the type that can be induced to attach to platelets (one patient) or both vWF abnormalities in different serial samples (one patient). In the one cardiac transplant patient who did not develop vWF multimeric abnormalities associated with thrombotic microangiopathy, vWF antigen levels were elevated more than threefold. This later individual received therapy with cyclosporin A alone. The other five thrombotic microangiopathy patients received cyclosporin A in combination with other chemotherapeutic agents (two patients); mitomycin-C, along with other chemotherapy (two patients); or multiple chemotherapeutic drugs, but not cyclosporin A or mitomycin C (one patient). The finding of vWF multimeric abnormalities during serial analysis of plasma samples from five of six patients with drug-associated thrombotic microangiopathy suggests the possibility that ULvWF forms derived from damaged or stimulated endothelial cells, along with the largest plasma vWF multimers, may be involved in the intravascular platelet clumping that is an essential part of the pathophysiology of this disorder.
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PMID:Abnormalities of von Willebrand factor multimers in drug-associated thrombotic microangiopathies. 843


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