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)

A total of 1,921 leukapheresis procedures have been performed on 532 normal and CML donors at six research institutions, for the purpose of supporting granulocytopenic leukemia patients during infectious episodes. The addition of HES alone or in combination with either etiocholanolone or dexamethasone, resulted in a significant increase in the numbers of leukocytes (granulocytes) harvested by continuous and noncontinuous flow centrifugation. Normal donors participating in these programs were monitored prior to and immediately following each procedure by standard laboratory methods which revealed no serious or abnormal changes occurring as a result of the procedure in those undergoing single or multiple donations with these agents. CML donors tolerated the addition of only HES well, as evidenced by the lack of toxic reactions in three donors undergoing 101 to 121 procedures.
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PMID:Hydroxyethyl starch as an experimental adjunct to leukocyte separation by centrifugal means: review of safety and efficacy. 5 17

A modified species of hydroxyethyl starch (HES 350/0.60) possessing a Mw- of 350,000 daltons combined with a molar hydroxyethyl group substitution (MS) of 0.60 (60 hydroxyethyl groups.100 glucose residues) was clinically assessed in seven normal subjects to determine the influence of these chemical modifications on intravascular clearance kinetics concomitantly with effects on the suspension stability (ESR) of blood. Following a standardised intravenous dose (30 gm.m2 BSA), the concentration of HES 350/0.60 in serum fell to half its peak value in 11.8 +/- 1.3 (SD) hours, while the ESR remained elevated for up to 12 hours post-injection. By adopting a Mw- of 350,000 daltons, the critical molecular weight (Cmw) of this colloid was surpassed, while the critical concentration (Cc), below which the suspension stability of blood is not affected, was shown to range between 0.3 and 0.5 gm.dl-1. In comparison to the present species of HES (Mw- 450,000 daltons, MS: 0.70) utilised as a sedimenting agent duirng centrifugal leucapheresis, HES 350,000/0.60 appears to affect the ESR in a similar manner, but is removed from the intravascular space approximately twice as rapidly. This more rapid clearance should be useful in avoiding cumulative build-up of HES in blood concomitant with reducing the total amount of intravascular H2O bound to this colloid, in normal and CML donors undergoing multiple cell collection procedures.
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PMID:The plasma kinetics of hydroxyethyl starch 350/0.60: a potential new adjunct for centrifugal leucapheresis. 9 71

Seven patients suffering from hypereosinophilic syndrome with clinical and/or hematological symptoms of a myeloproliferative syndrome were treated with a combination of hydroxyurea and interferon-alpha. To date, 6 of them have been followed for more than 1 year. In all cases, this therapy decreased circulating hypereosinophilia to under 1,500/mm3 and obtained normal eosinophil levels in 5 patients with a parallel regression of visceral complications. None of the patients experienced treatment-associated side effects, particularly hematological ones. Hypereosinophilic syndrome has a poor prognosis due, for the most part, to the development of visceral, cardiac and neurological complications, and, more secondarily, to the risk of progression towards acute leukemia. Conventional treatments, corticosteroids and hydroxyurea, have greatly improved the prognosis, but failure of these therapeutics remains common in the myeloproliferative form of the disease. Because interferon-alpha was proven to effectively treat chronic myeloid leukemia, it has been proposed for the treatment of hypereosinophilic syndromes, and encouraging results have been obtained despite the high daily doses required to control the disease. In the future, its association with hydroxyurea could represent an alternative therapy capable of controlling the disease at low doses thereby limiting the risk of side effects.
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PMID:[Treatment of hypereosinophilic syndromes of myeloproliferative expression with the combination of hydroxyurea and interferon alpha. Apropos of 7 cases]. 836 16

A 49-year-old man with the idiopathic hypereosinophilic syndrome (HES) and a unique chromosomal abnormality 46,XY,t(5;9)(q32;q33) is reported. Complete cytogenetic remission was induced by interferon alpha-2b (IFN-alpha). The beneficial action of IFN-alpha in different stem-cell disorders such as CML, HES, multiple myeloma and solid tumours such as hypernephroma or malignant melanoma suggests a common regulatory effect possibly by immunomodulation or other (immune-mediated) mechanisms, but the exact pathophysiological mechanisms remain hypothetic and unresolved. Since it has been known for some years that the genes encoding for GM-CSF, IL-3 and IL-5 reside on the long arm of chromosome 5, it could be possible that the chromosomal translocation in our patient resulted in excess production of these cytokines, hence causing the hypereosinophilia. This case report and the results obtained from the literature review support the growing body of evidence that IFN-alpha has a major place in the long-term treatment of HES, especially in those cases resistant to conventional treatment, with cytogenetic abnormalities, or presenting as a myeloproliferative variant of HES. In those cases IFN-alpha results in lower morbidity, lower mortality and long-term survival.
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PMID:Further evidence for the clonal nature of the idiopathic hypereosinophilic syndrome: complete haematological and cytogenetic remission induced by interferon-alpha in a case with a unique chromosomal abnormality. 921

Hypereosinophilic syndromes may result either from eosinophilic differentiation of a clone of neoplastic cells or from reactive eosinophilia. In other patients HES is idiopathic. It appears likely that in many patients the "idiopathic' hypereosinophilic syndrome is actually a chronic myeloproliferative disorder. Those cases showing an increase of blast cells or a demonstrable clonal cytogenetic abnormality should be classified as eosinophilic leukaemia. In other cases the neoplastic nature of the disease can be recognized only in retrospect when a granulocytic sarcoma or AMI, develops. A few cases of idiopathic HES are consequent on cytokine secretion whereas others remain idiopathic at the time of death. When eosinophilia occurs as a feature of an acute or chronic myeloid leukaemia or a chronic myeloproliferative disorder the eosinophils are usually part of the leukaemic clone. However, eosinophilia in association with acute lymphoblastic leukaemia is usually reactive. Rare cases have a biphenotypic leukaemia/lymphoma with both eosinophils and lymphoid cells arising from a mutant pluripotent stem cell.
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PMID:Eosinophilic leukaemias and the idiopathic hypereosinophilic syndrome. 885 31

Chromosomal aberrations have been reported in most malignant hematopoietic disorders such as acute or chronic myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndromes. Eosinophilic leukemia is a rare hematologic malignancy difficult to distinguish from other forms of idiopathic hypereosinophilic syndrome, so that the diagnosis is often made by exclusion, unless cytogenetic abnormalities can be demonstrated in bone marrow cells. We describe a patient with eosinophilic leukemia whose cytogenetic study shows a t(2;5)(p23;q31). Initial data could suggest a clonal eosinophilia, with an hepatosplenomegaly, severe pancytopenia, and a high level of blood and medullar eosinophilia.
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PMID:Eosinophilic leukemia associated with t(2;5)(p23;q31). 1194 46

Idiopathic hypereosinophilic syndrome (HES) is a myeloproliferative disease of unknown etiology. Recently, it has been reported that imatinib mesylate (Gleevec), an inhibitor of Bcr-Abl kinase useful in the treatment of chronic myeloid leukemia, is also effective in treating HES; however, the molecular target of imatinib in HES is unknown. This report identifies a genetic rearrangement in the eosinophilic cell line EOL-1 that results in the expression of a fusion protein comprising an N-terminal region encoded by a gene of unknown function with the GenBank accession number NM_030917 and a C-terminal region derived from the intracellular domain of the platelet-derived growth factor receptor alpha (PDGFRalpha). The fusion gene was also detected in blood cells from two patients with HES. We propose naming NM_030917 Rhe for Rearranged in hypereosinophilia. Rhe-PDGFRalpha fusions result from an apparent interstitial deletion that links Rhe to exon 12 of PDGFRalpha on chromosome 4q12. The fusion kinase Rhe-PDGFRalpha is constitutively phosphorylated and supports IL-3-independent growth when expressed in BaF3 cells. Proliferation and viability of EOL-1 and BaF3 cells expressing Rhe-PDGFRalpha are ablated by the PDGFRalpha inhibitors imatinib, vatalanib, and THRX-165724.
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PMID:Discovery of a fusion kinase in EOL-1 cells and idiopathic hypereosinophilic syndrome. 1280 48

Imatinib mesylate treatment is highly effective in chronic myeloid leukaemia and recent data have suggested that imatinib mesylate is also effective in the treatment of idiopathic hypereosinophilic syndrome (HES). Six patients with HES were treated daily with 100 mg imatinib mesylate. Five patients had normal karyotype and one showed trisomy 8. RT-PCR was negative for ETV6-PDGFRB and BCR-ABL fusion mRNAs. All patients rapidly achieved complete haematological remission. One patient remained in remission for more than 6 weeks after discontinuing treatment. No significant side effect was noted. Imatinib mesylate should be considered in the first-line therapy of idiopathic HES.
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PMID:Effective treatment of hypereosinophilic syndrome with imatinib mesylate. 1467 12

Idiopathic hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL) comprise a spectrum of indolent to aggressive diseases characterized by unexplained, persistent hypereosinophilia. These disorders have eluded a unique molecular explanation, and therapy has primarily been oriented toward palliation of symptoms related to organ involvement. Recent reports indicate that HES and CEL are imatinib-responsive malignancies, with rapid and complete hematologic remissions observed at lower doses than used in chronic myelogenous leukemia (CML). These BCR-ABL-negative cases lack activating mutations or abnormal fusions involving other known target genes of imatinib, implicating a novel tyrosine kinase in their pathogenesis. A bedside-to-benchtop translational research effort led to the identification of a constitutively activated fusion tyrosine kinase on chromosome 4q12, derived from an interstitial deletion, that fuses the platelet-derived growth factor receptor-alpha gene (PDGFRA) to an uncharacterized human gene FIP1-like-1 (FIP1L1). However, not all HES and CEL patients respond to imatinib, suggesting disease heterogeneity. Furthermore, approximately 40% of responding patients lack the FIP1L1-PDGFRA fusion, suggesting genetic heterogeneity. This review examines the current state of knowledge of HES and CEL and the implications of the FIP1L1-PDGFRA discovery on their diagnosis, classification, and management.
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PMID:The FIP1L1-PDGFRalpha fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management. 1554 34

According to the new WHO classification a group of chronic myeloproliferative diseases (CMPDs) were defined: chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia and hypereosinophilic syndrome (CEL/HES), polycythemia vera (PV), chronic idiopathic myelofibrosis (with extramedullary hematopoiesis, CIMF), essential thrombocythemia (ET), and so called CMPD/unclassifiable. As clinical features and laboratory findings differ widely between these diseases several diagnostic approaches are mandatory at diagnosis for classification and are needed also for follow up studies, especially for the measurement of minimal residual disease (MRD). We here outline the laboratory set up at diagnosis and during follow up in CMPDs with specific focus on the respective therapeutical consequences. Only by using a comprehensive diagnostic panel including cytomorphology, cytogenetics, and molecular genetic methods establishing the correct diagnosis, optimizing treatment as well as evaluating treatment response is possible in CMPDs today.
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PMID:Modern diagnostics in chronic myeloproliferative diseases (CMPDs). 1512 74


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