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 novel erythroid cell line, RM10, was established from a long-term bone marrow culture of a patient with chronic myelogenous leukemia (CML). RM10 cells were positive for periodic acid Schiff (PAS), but negative for peroxidase and dual esterase. RM10 cells had la, pre B (CD10), myeloid (CD13, CD14, CD33) and erythroid (glycophorin A) markers, but had no other lymphoid, megakaryocytic, or mesenchymal cell markers. RM10 cells spontaneously synthesized hemoglobin, which was markedly enhanced with hemin. Isoelectric focusing of the cell lysates and northern blot analysis of the total cellular RNA revealed hemoglobin synthesis in the cells. Using 125I-labeled recombinant human erythropoietin (Epo), two classes of Epo receptors were demonstrated in the RM10 cells. However, Epo did affect neither growth nor erythroid differentiation of the cells. RM10 cells rapidly differentiated to monocytic cells in the presence of 12-0-tetradecanoylphorbol-13-acetate, and simultaneously expressed glycoprotein IIb/IIIa. RM10 cells had Philadelphia chromosome (Ph), and expressed p210bcr-abl using immunoprecipitation with anti-c-abl and anti-phosphotyrosine antibodies. These results indicate that the RM10 cells have the characteristics of multipotential hemopoietic cells originating from Ph-positive CML and that high affinity Epo receptor class is not a sufficient condition for Epo responsiveness.
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PMID:A novel CD10-positive erythroid cell line, RM10, established from a patient with chronic myelogenous leukemia. 216 10

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

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

To determine whether distinct subpopulations of platelets exist in individual patients, platelets were incubated with monoclonal antibodies to glycoprotein Ib and the glycoprotein IIb-IIIa complex, and analyzed by flow cytometry. Normal donors (n = 15) had single glycoprotein Ib-positive and glycoprotein IIb-IIIa complex-positive populations of platelets, with no subpopulations. In normal donors there was a direct relationship between platelet size and the number of surface glycoprotein Ib and glycoprotein IIb-IIIa complex antigens per platelet. In patients with Bernard-Soulier syndrome and Glanzmann's thrombasthenia, all platelets were equally negative with regard to the glycoprotein Ib and glycoprotein IIb-IIIa complex phenotype, respectively. In contrast, each of six children with chronic myeloid leukemia (four of whom were Philadelphia chromosome negative and two of whom were Philadelphia chromosome positive) had two phenotypically distinct subpopulations of platelets: one glycoprotein Ib negative, the other glycoprotein Ib positive. In each of these six children with chronic myeloid leukemia, phenotypically distinct subpopulations of glycoprotein IIb-IIia complex-negative and glycoprotein IIb-IIIa complex-positive platelets were also detected. Polyclonal antiplatelet antibody bound to both the glycoprotein Ib-negative and glycoprotein IIb-IIIa complex-negative subpopulations. Age-matched controls (n = 3) and adults with Philadelphia chromosome-positive chronic myeloid leukemia (n = 3) showed single glycoprotein Ib-positive and glycoprotein IIb-IIIa complex-positive populations. In conclusion, flow cytometry detected distinct subpopulations of platelets in children with chronic myeloid leukemia. Flow cytometry is an important new method of identification and investigation of subpopulations of platelets in individual patients.
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PMID:Flow cytometric analysis of platelet surface glycoproteins: phenotypically distinct subpopulations of platelets in children with chronic myeloid leukemia. 347 97

A 64-yr-old Japanese man presented with mild anemia, leukocytosis, and thrombocytosis in November 1999. A diagnosis of chronic myeloid leukemia was made with a positive Ph chromosome, and interferon alpha treatment was started, 6 million units a day. Two years later, in October 2001, the patient developed leukocytosis, an increased LDH level, and large blasts with basophilic cytoplasm with cytoplasmic projections appeared in the peripheral blood. Bone marrow aspiration revealed increased blasts (59.6%). These blasts were negative on peroxidase stain, positive on acid phosphatase, and weakly positive on alpha naphthyl butyrate esterase stain and periodic acid-Schiff stain. Immunohistochemical staining with monoclonal antibodies revealed that these blasts were strongly positive with anti-CD41 (glycoprotein IIb/IIIa), weakly positive with CD7, CD33, and CD34, and negative with other monoclonal antibodies. A diagnosis of megakaryoblastic transformation from chronic myeloid leukemia was therefore made. Two-color fluorescence in situ hybridization (FISH) for portions of the major-bcr and abl genes from bone marrow cells revealed two fused signals in 90.6% and one fused signal in 5.8% of 106 cells. A cytogenetic study revealed that bone marrow cells were 69, XYY, +6, -7, +8, -9, t(9;22)(q34;q11), +11, +13, -15, -16, dic(17;18)(p11;p11), -18, +19, +21, der(22)t(9;22) in six of nine examined cells. These findings confirmed that these megakaryoblasts originated from megakaryocytes of the chronic myeloid leukemia clone.
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PMID:Double Ph-positive megakaryoblastic transformation of chronic myeloid leukemia. 1236 19

3-Hydrogenkwadaphnin (3-HK) is a daphnane-type diterpene ester isolated from Dendrostellera lessertii (Thymelaeaceae) with high differentiation and apoptotic potency in leukemic cells without any measurable adverse effects on normal cells (Moosavi et al., 2005b). In this study, we report that 3-HK (12 nM) has the ability to cease proliferation, induce differentiation and apoptosis in chronic myelogenous leukemia (CML) K562 cell line. The treated cells lost erythroid properties and differentiated along the megakaryocytic lineage based on the morphological features apparent after Wright-Giemsa staining, DNA content analysis and the expression of cell surface marker glycoprotein IIb as analyzed by flow cytometry. Moreover, using Hoechst 33258 and Annexin V double staining indicated the occurrence of apoptosis among the treated cells. On the other hand, restoration of the depleted GTP pool size by exogenous addition of guanosine (50 microM) reduced the effect of the drug regarding the extent of differentiation while no further enhancement of 3-HK effect was obtained by addition of exogenous hypoxanthine (100 microM). These interesting results necessitate further investigation regarding the mechanism of action of this unique anti-leukemic agent.
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PMID:Induction of megakaryocytic differentiation in chronic myelogenous leukemia cell K562 by 3-hydrogenkwadaphnin. 1804 90

Chronic Myelogenous Leukemia (CML) is a myeloproliferative neoplasm characterized by proliferation of Philadelphia positive clonal pluripotent hematopoietic cells. Bleeding is a rare presentation of CML that can occur due to platelet dysfunction. Both pre-treatment and post-treatment platelet function abnormalities in CML have been described in the literature. We describe a rare case of childhood CML who presented with mucocutateous bleeding manifestations. On laboratory workup, a Glanzmann Thrombasthenia (GT) like platelet phenotype was demonstrated along with confirmation of diagnosis of CML in chronic phase. The acquired nature of platelet function defect was confirmed by demonstrating recovery of platelet antigens glycoprotein IIb/IIIa after achieving complete hematological response with Imatinib. Due to presenting complaint of bleeding diathesis and absence of hepatosplenomegaly, the case was undiagnosed for CML until the patient reported to us. Careful evaluation of complete blood counts, peripheral blood picture and detailed laboratory workup was the window to proper diagnosis and treatment in this case.
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PMID:Reversal of Glanzmann thrombasthenia platelet phenotype after imatinib treatment in a pediatric chronic myeloid leukemia patient. 2918 19