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)

In this study we have investigated the relationship between the labelling index of plasma cells, the expression of CD38 positive lymphocytes in the peripheral blood, and light chain isotype suppression. This study confirms the relationship between plateau-phase disease and light chain isotype suppression (LCIS) and documents an inverse relationship between LCIS and CD38 positive lymphocytes (.001 less than P less than .01), which is similar to the relationship we have described with the expression of CD10 positive lymphocytes. PCA-1 is rarely expressed in the peripheral blood of patients with myeloma and does not fulfill a role as a marker of active vs. stable disease. There is no relationship between the labelling index of plasma cells and LCIS, because many patients can enter a stage of progressive disease and yet have a labelling index of less than 1% at that time, although a labelling index less than 1% is present in the majority of patients with LCIS. beta-2-microglobulin (beta 2M) also fails to differentiate these two phases of disease in myeloma and does not have a relationship with LCIS, CD38 expression, or CD10 expression. These data suggest that myeloma, like chronic granulocytic leukemia (CGL), can be considered as having two phases of disease: a stable or chronic phase disease, as identified by the presence of LCIS, the absence of CD10 and CD38 positive lymphocytes in the peripheral blood, and a low labelling index, and progressive disease, which is associated with the loss of LCIS and of, CD10 and CD38 positive lymphocytes in the peripheral blood and a high labelling index, although in many cases of progressive disease, the labelling index may also be low. beta 2M does not differentiate between these states.
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PMID:Multiple myeloma: relationship between light chain isotype suppression, labelling index of plasma cells, and CD38 expression on peripheral blood lymphocytes. 305 44

The fate of beta-2-microglobulin was investigated in 17 patients with chronic myeloid leukemia by correlation analysis of the plasma concentration and various clinical measurements. The plasma concentration of beta-2-microglobulin correlated individually with white blood cell count, differential counts of band and segmented neutrophils, metamyelocytes and myelocytes, and haptocorrin concentration during the clinical course (p less than 0.002). The neutrophil granulocytes from the differential stage of myelocytes appears to be a major source of beta-2-microglobulin in chronic myeloid leukemia, and our results suggest that beta-microglobulin is is contained within the specific granules or is liberated from the plasma membranes synchronously with degranulation of neutrophils.
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PMID:Serial measurements of beta-2-microglobulin in plasma correlates with white blood cell counts and haptocorrin in chronic myeloid leukemia. 331 27

This report aims to review briefly the current status of treatment of haematological malignancies with interferon-alpha (IFN-alpha). Overall hairy cell leukemia and chronic myelogenous leukemia appear to be most sensitive to IFN-alpha. We started to investigate, how interferon exerts its antileukemic activity and in which way interferon therapy can be optimized. Our preliminary results fail to support the view of interferon mediated enhancement of host responses. They rather indicate direct effects of IFN on leukemic cells in vitro. By means of IFN-dependent biological markers (e.g. beta-2-microglobulin, neopterin) clinically effective but atoxic doses of IFN-alpha could be defined for HCL and CML. In final conclusion, the recent studies on the clinical efficacy of IFN-alpha revealed its potent antitumoral effect in hematological malignancies. However, the further proof of the potential benefit of IFN treatment versus conventional therapeutic strategies remains to be elucidated.
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PMID:[Interferon-alpha in the treatment of hematologic neoplasms]. 352 22

The regulation of Ia (HLA-DR) antigen expression on myeloid progenitor cells may be closely related to the control of myelopoiesis in both normal individuals and chronic myeloid leukemia (CML) patients. In an effort to study directly the expression and behavior of Ia surface molecules on myeloid progenitor cells, we used an immunologic purification technique to enrich these cells approximately 100-fold from the peripheral blood of CML patients. The majority of cells in this blast population expressed HLA-DR antigens. Thirty percent to 40% of cells could form a granulocyte or monocyte colony in agar, and these cells tended to express the highest levels of HLA-DR. The number of HLA-DR molecules per cell increased about twofold as the cells tranversed the cell cycle from G0/G1 to G2/M. This was true for unstimulated cells or cells exposed to colony-stimulating factors. Some of this increase was related to a corresponding increase in cell size and is also seen with other cell surface antigens such as beta-2-microglobulin. Ia antigen expression was not modified by culture with colony-stimulating factors, fetal calf serum, or serum-free, prostaglandin-free medium for periods of up to 24 hours. These results demonstrate that Ia antigens are expressed on the myeloid progenitor cells of CML, are increased in the S and G2/M phases of the cell cycle, and are stable under most in vitro culture conditions for at least 24 hours of culture.
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PMID:Expression of Ia antigens on myeloid progenitor cells in chronic myeloid leukemia: direct analysis using partially purified colony-forming cells. 385 62

It was the aim of this study to investigate the antileukemic activities of recombinant interferon beta (rIFN beta) in chronic-phase CML in vitro and in vivo. Nine patients in the early chronic-phase of CML were treated in a phase-II trial with escalating doses of rIFN beta. In parallel, antiproliferative and immunomodulatory activities of rIFN beta and rIFN alpha 2b were studied in vitro. rIFN beta exhibited a significantly higher antiproliferative activity on hematopoietic progenitor cells of CML patients in vitro than rIFN alpha 2b. In contrast, only very limited clinical antileukemic efficacy of rIFN beta was observed. None of the patients achieved a complete or partial hematologic response (0% response rate, 0-36% 95 C.I.). Primary resistance of CML patients to rIFN beta treatment was caused neither by antibody formation against the recombinant material nor by deficient IFN receptor targeting and/or signaling; Induction of serum levels of beta-2-microglobulin (beta-2-m) and neopterin after administration of rIFN beta was comparable to that seen after administration of rIFN alpha. However, rIFN beta treatment less effectively induced biosynthesis of interleukin-1 receptor antagonist protein (IL-1-Ra) than rIFN alpha 2b. Thus, we conclude that rIFN beta at doses up to 12 MU/day s.c. is ineffective for treatment of chronic-phase CML. Further investigations into divergent biologic responses to various type-I interferons might help to elucidate mechanisms crucial for IFN action in patients with CML.
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PMID:Divergent in vivo and in vitro antileukemic activity of recombinant interferon beta in patients with chronic-phase chronic myelogenous leukemia. 769 61

The investigation of cell composition and different biochemical parameters (ceruloplasmin, lactate dehydrogenase, aldolase, ferritin, beta-2-microglobulin) in cerebrospinal fluid has been performed in 37 patients with chronic myeloid leukemia at different clinicohematological stages. The age of the patients ranged from 16 to 67 years. CNS involvement has been diagnosed in 8 (21.6%) patients by clinical and cytological criteria and in 5 (13.5%) patients on the basis of changes in liquor cytograms and in biochemistry. Morphological substrate of leukemic infiltration may be represented by blast cells and cells of granulocytic line of all stages of differentiation. Direct correlation has been established between ferritin and beta-2-microglobulin levels in liquor and its cytological patterns. This permits a conclusion on possible usage of liquor concentration of beta-2-microglobulin and ferritin measurements as additional tests in the diagnosis of neuroleukemia in chronic myeloid leukemia.
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PMID:[The cytological and biochemical aspects of studying the cerebrospinal fluid in patients with chronic myeloleukemia]. 821 76

We compared the effect of control genes (CG): total Abelson (total-ABL), beta-2-microglobulin (B2M) and beta-glucuronidase (GUS), recommended in the Europe Against Cancer (EAC) program, on real-time BCR-ABL monitoring in patients with chronic myeloid leukemia (CML). We focused on the stability of CG expressions during therapy and the effect of the CGs on BCR-ABL ability to characterize the disease status and disease prognosis, issues that have not been addressed yet. The results showed B2M as a very convenient CG for BCR-ABL monitoring. On the contrary, the widely used total-ABL was not confirmed as appropriate for normalization of gene expression in CML.
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PMID:The effect of total-ABL, GUS and B2M control genes on BCR-ABL monitoring by real-time RT-PCR. 1751 89

Genetic linkage analyses, genome-wide association studies of single nucleotide polymorphisms, copy number variation surveys, and mutation screenings found the human chromosomal 12q24 locus, with the genes SH2B3 and ATXN2 in its core, to be associated with an exceptionally wide spectrum of disease susceptibilities. Hematopoietic traits of red and white blood cells (like erythrocytosis and myeloproliferative disease), autoimmune disorders (like type 1 diabetes, coeliac disease, juvenile idiopathic arthritis, rheumatoid arthritis, thrombotic antiphospholipid syndrome, lupus erythematosus, multiple sclerosis, hypothyroidism and vitiligo), also vascular pathology (like kidney glomerular filtration rate deficits, serum urate levels, plasma beta-2-microglobulin levels, retinal microcirculation problems, diastolic and systolic blood pressure and hypertension, cardiovascular infarction), furthermore obesity, neurodegenerative conditions (like the polyglutamine-expansion disorder spinocerebellar ataxia type 2, Parkinson's disease, the motor-neuron disease amyotrophic lateral sclerosis, and progressive supranuclear palsy), and finally longevity were reported. Now it is important to clarify, in which ways the loss or gain of function of the locally encoded proteins SH2B3/LNK and ataxin-2, respectively, contribute to these polygenic health problems. SH2B3/LNK is known to repress the JAK2/ABL1 dependent proliferation of white blood cells. Its null mutations in human and mouse are triggers of autoimmune traits and leukemia (acute lymphoblastic leukemia or chronic myeloid leukemia-like), while missense mutations were found in erythrocytosis-1 patients. Ataxin-2 is known to act on RNA-processing and trophic receptor internalization. While its polyglutamine-expansion mediated gain-of-function causes neuronal atrophy in human and mouse, its deletion leads to obesity and insulin resistance in mice. Thus, it is conceivable that the polygenic pathogenesis of type 1 diabetes is enhanced by an SH2B3-dysregulation-mediated predisposition to autoimmune diseases that conspires with an ATXN2-deficiency-mediated predisposition to lipid and glucose metabolism pathology.
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PMID:12q24 locus association with type 1 diabetes: SH2B3 or ATXN2? 2493 53