Leukemia research
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A clonal origin of hematopoiesis was studied by investigation of X-chromosome inactivation patterns (XCIP) in isolated granulocyte, CD14(+) and CD3(+) subpopulations obtained from bone marrow and peripheral blood of 36 female patients with primary myelodysplastic syndrome (MDS). Clonality was assessed by PCR amplification of polymorphic short tandem repeats of the human androgen receptor (HUMARA) gene and by investigation of silent polymorphism of iduronate sulphatase (IDS) or p55 genes. On the basis of results in a control group of 20 healthy age related females, a ratio of at least 9:1 between the two alleles was considered a significant marker of monoclonal hematopoiesis. ⋯ Despite some limitations, the measurement of XCIP remains a sensitive tool for diagnosis of the first transforming mutation in the clonal development of MDS especially when combined with FISH and when an age related group is used to establish an appropriate allele ratio to exclude constitutional or acquired skewing. The occurrence of clonal cell subpopulations in most of the RCMD patients in contrast to RA may reflect a proposed multistep pathogenesis of MDS with dysplastic changes limited to erythropoiesis in early step and with subsequent development of multilineage dysplasia. The results also support the usefulness of separation of RCMD from 'pure' RA; however, a more complex insight combining different molecular techniques performed in a large number of patients is needed for refined classification of MDS on the basis of new molecular prognostic factors and for indication of more effective targeted therapy.
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P27 encodes a member of Cip/Kip family of cyclin dependent kinase inhibitors, the inactivation of which has been implicated in the pathogenesis of various hematological neoplasias. We report on a novel point mutation of this gene identified in a case of unclassified myeloproliferative syndrome consisting of a T --> C transversion at 821bp of p27 exon 1, resulting in a Ile --> Thr substitution at codon 119. The analysis of larger number of cases as well as the effect of this mutation on protein's function will help to clarify its significance in the pathogenesis of myeloproliferative syndromes.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
A phase III, randomized, double-blind, placebo-controlled, study of iseganan for the reduction of stomatitis in patients receiving stomatotoxic chemotherapy.
The invasion and colonization of oral cavity mucosal tissues by microflora may contribute to the pathophysiology of ulcerative oral mucositis (UOM). Iseganan is an analog of protegrin-1, a naturally occurring peptide with broad-spectrum microbicidal activity. A randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of iseganan in preventing UOM after stomatotoxic therapy. ⋯ Forty-three percent and 37% of iseganan and placebo patients, respectively, did not have peak stomatitis grade =2 (P = 0.182). There was no significant difference between the cohorts in stomatitis severity, incidence of UOM, peak mouth pain, peak difficulty swallowing, amount of opiate analgesics used, or adverse event type or incidence. A major impact of Iseganan on reducing stomatitis, UOM, or its clinical sequelae in patients receiving stomatotoxic therapy was not detected on this study.
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Imatinib mesylate (STI571) is a major therapeutic advance for the management of chronic myeloid leukaemia (CML), however, a proportion of patients are refractory to it, particularly those in more advanced phases of CML. Different mechanisms of resistance to imatinib are suggested, including point mutations within ABL-kinase domains. ⋯ Additionally, clonal evolution could lead to BCR-ABL-independent proliferation. Early detection of ABL-kinase mutation could predict the progression of CML treated with imatinib.