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

The expansion of the Philadelphia (Ph) chromosome positive clone in chronic myeloid leukemia (CML) may depend on its capacity to suppress the proliferation of Ph-negative stem cells, but this proliferative advantage might, in certain circumstances, be reversible. Various lines of evidence suggest that Ph-negative cells, albeit in a suppressed state, must still be present. As recently suggested, the expansion of 'putative' normal Ph-negative hemopoietic stem cells might have, in certain circumstances, a proliferative advantage over the Ph clone in CML. This suggests that the treatment of CML with intensive chemotherapy might allow the collection of Ph-negative hemopoietic cells in the early phase of recovery. Eight patients with acute phase chronic myelogenous leukemia (AP-CML) were treated with idarubicin, intermediate dose cytarabine and etoposide. During recovery from bone marrow aplasia, when the white blood cell count reached 0.3-1 x 10(-9), blood cells were collected with 2-5 (median 3) consecutive leukapheresis. In 5/8 patients, these peripheral cells were Ph-negative at the cytogenetic analysis. Moreover, in one case the polymerase chain reaction analysis performed to detect the presence of minimal residual disease in the cells collected by leukapheresis was negative, further confirming that this approach may induce a very high degree of suppression of the Ph-positive clones. After complete recovery, these five patients were subsequently treated with high-dose etoposide, cyclophosphamide and total body radiation (10 Gy, single dose) followed by reinfusion of Ph-negative peripheral blood stem cells. All these patients received cyclosporine A post-autotransplant in an attempt to induce acute graft-versus-host-disease. Three of 5 patients remain in clinical and cytogenetic remission 5-15 months post-transplant. It is concluded that Ph-negative peripheral blood stem cells can be recovered from patients with AP-CML and used successfully to restore Ph-negative hemopoiesis after high dose therapy.
Leukemia 1991 Jun
PMID:Therapy of acute phase chronic myelogenous leukemia with intensive chemotherapy, blood cell autotransplant and cyclosporine A. 167 80

Ten leukemic patients were treated with allogeneic bone marrow transplantation (BMT). The diagnosis were ANLL in 6 cases, CML in 3 and ALL in one. Pretransplant immuno suppressive measures including total body irradiation cyclophosphamide and daunorubicin were given. All the patients were infused with health stem cell preparation, so that the hemopoietic function was restored. Graft versus-host disease of grade I to II was present in 5 of the patients. Leukemia recurred 76 days after BMT in one patient who received the procedure during a relapse of the disease, while in the remaining 9 patients disease-free survival from 1 to 23 months has been observed.
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PMID:[Allogeneic bone marrow transplantation in the treatment of leukemia: analysis of 10 cases]. 168 16

We have previously shown that maturing neoplastic cells from patients with stable phase chronic myelogenous leukemia (SP CML) constitutively produce granulocyte colony-stimulating factor (G-CSF) and are also receptive for this molecule. G-CSF functions as an endogenous growth factor in SP CML, and thus is responsible for divisions in maturing leukemic cells leading to an expansion of the compartment of mature cells. In the investigations to be reported below, the effects of various hematopoietic inhibitor molecules on the expression of the G-CSF gene by SP CML bone marrow cells enriched for promyelocytes/myelocytes were examined at the mRNA and protein level. We show that exposure of SP CML bone marrow promyelocytes/myelocytes to recombinant human (rh) interferon (IFN)-gamma but not to rh IFN-alpha, rh tumor necrosis factor (TNF)-alpha, and rh lymphotoxin (LT) leads to downregulation of G-CSF expression and interruption of the G-CSF-mediated endogenous growth stimulation. The action of G-CSF takes place at the posttranscriptional level and involves an acceleration of decay of steady-state levels of G-CSF transcripts in the malignant cell population.
Leukemia 1990 Nov
PMID:Gamma-interferon interrupts growth stimulation in chronic myelogenous leukemia established by endogenous granulocyte colony-stimulating factor. 170 Feb 39

The interactions between haemopoietic progenitor cells and marrow stromal cells that are essential for the regulation of normal haemopoiesis are defective in chronic phase chronic myeloid leukaemia (CML). The presence of primitive progenitor cells (blast colony-forming cells, Bl-CFC) in the blood of patients with CML is reflected by their reduced capacity to bind to marrow derived stromal layers in vitro. Whereas normal bone marrow Bl-CFC bind irreversibly to cultured stromal layers (and none are found in normal blood), the Bl-CFC in CML bind transiently and then detach. The normal cell adhesion mechanism is partially sensitive to treatment with phosphatidylinositol-specific phospholipase C (Pl-PLC), indicating the participation of a phosphatidylinositol (Pl)-linked structure; however, when CML cells were treated with Pl-PLC it had no effect on progenitor binding. Two other Pl-linked structures, decay-accelerating factor (DAF) and lymphocyte function associated antigen-3 (LFA-3) were normally expressed on CD34 positive CML cells and normally susceptible to Pl-PLC treatment. The treatment of normal cells with Pl-PLC, to mimic the situation in CML, resulted in the indiscriminate and inefficient binding of Bl-CFC to stroma. Moreover, treatment of the normal cells with 5637 conditioned medium (CM), which contains haemopoietic growth factors, also reduced the binding capacity of normal Bl-CFC; 5637CM treatment did not alter the expression of DAF. It is proposed that a Pl-linked cell adhesion molecule (CAM) is deficient in CML as a consequence of the constitutive activation of ABL kinase whilst, in normal cells, CAMs attached in this manner are responsible for efficient adhesion to stroma and are regulated by growth factors.
Leukemia 1991 Aug
PMID:Deficiency of a phosphatidylinositol-anchored cell adhesion molecule influences haemopoietic progenitor binding to marrow stroma in chronic myeloid leukaemia. 171 60

A monoclonal antibody (17F11) was raised by immunization of a Balb/c mouse with leukemic blasts from a patient with acute non-lymphocytic leukemia (ANLL). This antibody recognizes most leukemic blasts of myeloid but not of lymphoid lineage and no peripheral blood cells. By screening NIH-3T3 fibroblasts transfected with the human proto-oncogene c-kit (NIH-3T3/hckit) it could be shown that 17F11 specifically recognizes the gene product P145c-kit. Immunofluorescence analysis on normal hemopoietic cells revealed that 17F11 weakly stains 1-3% of bone marrow mononuclear cells (BMMNC). By FACS sorting and colony assays it could be shown that granulocyte--macrophage progenitor cells could be enriched 10-20-fold, granulocyte progenitors 50-80-fold, and erythroid and multipotential progenitor cells 15-20-fold, in the 17F11 positive fraction. Double fluorescence analysis revealed that P145c-kit is co-expressed on 40-60% of the CD34 positive BMMNC. Finally, these data show that P145c-kit is expressed on blast cells from most patients with ANLL (26/30) and chronic myeloid leukemia in blast crisis (7/9), but is absent on blasts from patients with acute lymphoblastic leukemia expressing the T-, B-lineage, or common ALL phenotypes.
Leukemia 1991 Oct
PMID:The product of the proto-oncogene c-kit (P145c-kit) is a human bone marrow surface antigen of hemopoietic precursor cells which is expressed on a subset of acute non-lymphoblastic leukemic cells. 172 Apr 90

Monoclonal antibody QBEND10 is reactive with the CD34 antigen in aldehyde-fixed, decalcified, paraffin-embedded bone marrow biopsies. In normal bone marrow it stained endothelial cells lining arterioles and capillaries, sinusoidal (littoral) cells and 0.89% of all haemopoietic cells. QBEND10+ mononuclear cells were seen as isolated, randomly distributed mononuclear cells in normal and regenerating bone marrows. Conversely, QBEND10+ cells were increased and present in aggregates of three or more cells in 6/8 cases of acute leukemia; in two cases of CD34-negative leukemia and in two patients after complete remission no aggregates were seen. QBEND10 immunohistochemistry may therefore be useful for diagnosis and follow-up of myeloid leukemias. In addition, increased numbers of CD34+ cells arranged in clusters were seen in 4/9 cases of refractory anemia with excess blasts (RAEB), 1 case of chronic myelomonocytic leukemia, 3/3 cases of RAEB in transformation, and in 3/7 cases of chronic myelogenous leukemia: in all these cases, CD34 staining of the bone biopsy may have prognostic value. QBEND10+ endothelial cells were significantly increased in all the pathological conditions examined (1.43% of all nucleated cells versus 0.80% in normal bone marrow; p = 0.0063), but especially in myeloid leukemias and in two fibrotic syndromes examined.
Leukemia 1991 Dec
PMID:Identification of CD34+ cells in normal and pathological bone marrow biopsies by QBEND10 monoclonal antibody. 172 30

By using antisense oligomers the functional role of the c-abl proto-oncogene in the in vitro growth of bone marrow hematopoietic progenitors from normal subjects and patients with chronic myelogenous leukemia (CML) has been evaluated. Light density bone marrow cells (LDBMs) were depleted of adherent cells, pre-incubated for 15 h with the appropriate oligomer at a concentration of 14 microns, and then plated in methylcellulose for the evaluation of colony formation. Both anti-exon Ia and anti-exon Ib antisense oligomers produced a significant inhibition of normal day 14 CFU-GM growth in vitro (n = 5, 41 +/- 11%, and 36 +/- 7%, respectively; p less than 0.01). In contrast, normal BFU-E growth was not significantly influenced by antisense oligomers (n = 5, 14 +/- 21% and 7 +/- 19%, respectively; p less than 0.05). These findings were confirmed by plating CD34 positive progenitors. When interleukin 3 (IL-3) (100 ng/ml) was added to the culture medium during the preincubation of LDBMCs, the inhibitory effects of antisense oligomers on normal CFU-GM growth were abolished. Seven patients with CML were also studied, all of whom had cytogenetic evidence of 100% clonal hematopoiesis. In five patients in the chronic phase, antisense oligomers were inhibitory on in vitro growth of both day 14 CFU-GM (37 +/- 20% and 37 +/- 15%, p less than 0.05) and BFU-E (45 +/- 15% and 41 +/- 11%, p less than 0.05), and this inhibition was not removed by pre-incubation with IL-3. No significant effect was observed on cluster or colony formation in two patients with CML in accelerated or blastic phase, and on in vitro growth of clonogenic cells from the Ph1-positive K-562 cell line. These findings (i) confirm previous observations showing a lineage specific requirement of c-abl function in normal hematopoiesis, and (ii) suggest that the residual c-abl expression has a role in chronic phase CML hematopoiesis, as its inhibition impairs both myeloid and erythroid colony formation in vitro.
Leukemia 1992 Jan
PMID:c-abl function in normal and chronic myelogenous leukemia hematopoiesis: in vitro studies with antisense oligomers. 173 9

A sensitive and specific serum marker can greatly help in the early diagnosis of malignancy as well as in monitoring the treatment of cancer patients. The present work was initiated for determining serum levels of Total Sialic Acid (TSA), Lipid Bound Sialic Acid (LSA), Free Sialic Acid (FSA). Regan Isoenzyme (RI) and Lactate Dehydrogenase (LDH), so as to evaluate their value as potential tumor markers. Fifty patients with anemia and 78 patients with leukemia were studied. The leukemia group consisted of 32 cases of Acute Myeloid Leukemia (AML), 29 cases of Chronic Myeloid Leukemia (CML) and 17 cases of Acute Lymphatic Leukemia (ALL). The levels were compared with the values obtained from 88 healthy individuals. Compared to the healthy controls, all the biomarkers were significantly elevated in patients with anemia as well as in those with leukemia. However, in leukemia patients significantly higher levels of TSA, LSA, FSA and LDH were observed compared to anemia patients. TSA levels were significantly higher in AML patients compared to CML and ALL patients. LSA levels were also significantly higher in AML patients compared to ALL patients. LSA was the most sensitive (84.6%) while FSA and RI levels were the most specific (78.0%) markers for leukemia. The combined use of the markers showed increased sensitivity and specificity (100.0% and 98.0%, respectively). The study suggested that the biomarkers investigated might be used for differentiating anemic from leukemic conditions, however, more in-depth studies are indicated to assess their utility in classifying various leukemias.
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PMID:Tumor markers in leukemia: evaluation of serum levels of different forms of sialic acid, Regan isoenzyme and lactate dehydrogenase. 179 11

The configuration of the T-cell receptor (TCR) beta, gamma and delta chain genes was analyzed in 16 cases of B-lymphoid blastic crisis of chronic myeloid leukemia (BC-CML) for a better definition of the biological aspects of this cellular population, in comparison with the molecular features of B-precursor acute lymphoblastic leukemia (ALL). All cases displayed B-phenotypic features, were Ph'-positive and had a rearranged configuration of the breakpoint cluster region (bcr) and of the immunoglobulin heavy chain gene region (JH). The TCR beta chain gene was rearranged in four cases (25%), all of which displayed a monoallelic rearrangement involving the J beta 2 region. The TCR gamma chain gene was rearranged in 13 cases (81%); 13 rearranged alleles utilized the J1/2 regions, while the remaining five utilized JP1. The V regions of the group I were mostly involved. The TCR delta chain gene was rearranged or deleted in 15 cases (94%); the 10 rearranged chromosomes displayed exclusively two patterns referable to partial recombinations, a V2-(D)-D3 and a (D)-D3 type. These two configurations are predominant in B-precursor ALL (75% of rearranged chromosomes) and almost absent in T-ALL. Taken together, these results document the close similarities between the genotypic features of B-lymphoid BC-CML and B-precursor ALL, not only in terms of the incidence of rearrangement but more relevantly with regard to the choice of regions involved in the recombinations. This aspect is particularly evident at the TCR delta locus level.
Leukemia 1991 May
PMID:Identical utilization of T-cell receptor gene regions in B-lymphoid blast crisis of chronic myeloid leukemia and B-precursor acute lymphoblastic leukemia. 182 53

To determine the role of the BCR-ABL gene in the proliferation of blast cells of patients with chronic myelogenous leukemia, leukemia blast cells were exposed to synthetic 18-mer oligodeoxynucleotides complementary to two identified BCR-ABL junctions. Leukemia colony formation was suppressed, whereas granulocyte-macrophage colony formation from normal marrow progenitors was unaffected. When equal proportions of normal marrow progenitors and blast cells were mixed, exposed to the oligodeoxynucleotides, and assayed for residual colony formation, the majority of residual cells were normal. These findings demonstrate the requirement for a functional BCR-ABL gene in maintaining the leukemic phenotype and the feasibility of gene-targeted selective killing of neoplastic cells.
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PMID:Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides. 185 87


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