157 research outputs found

    Deep and early molecular response induced by nilotinb in a newly diagnosed patient with chronic myeloid leukemia (CML)

    Get PDF
    We report a case of a patient with chronic myeloid leukemia diagnosed in January 2012 and treated with nilotinib 600 mg/die as first line therapy. Patient obtained a complete hematologic response (CHR) and improvement of splenomegaly in 2 weeks. In three months the patient obtained complete cytogenetic response (CCR) and an important transcript level reduction (less than 1%). According to the international recommendations, molecular analysis was performed every three months in a LABNET network laboratory. Treatment was never interrupted or reduced due to any adverse event. After 9 months patient achieved a major molecular response (MMR) and during evaluation a MR4 has been documented

    Nilotinib therapy after resistance and intolerance to imatinib in CML patient with trisomy of the chromosome 8

    Get PDF
    In this article is presented the case of a 30-year-old woman with chronic myeloid leukaemia (CML) treated with imatinib for 15 months, and then with nilotinib as second-line therapy. Two episodes of grade 3 neutropenia, the detection of the trisomy of chromosome 8 and the failed achievement of a major molecular response (MMolR) in 15 months led to the switch to nilotinib. With nilotinib the patient obtained the lack of the genetic anomaly in 3 months and a complete molecular response (CMolR) in 6 months, all confirmed at 9 months. No haematologic or extra-haematologic adverse events were detected with this second-line agent

    Non random distribution of genomic features in breakpoint regions involved in chronic myeloid leukemia cases with variant t(9;22) or additional chromosomal rearrangements

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The t(9;22)(q34;q11), generating the Philadelphia (Ph) chromosome, is found in more than 90% of patients with chronic myeloid leukemia (CML). As a result of the translocation, the 3' portion of the <it>ABL1 </it>oncogene is transposed from 9q34 to the 5' portion of the <it>BCR </it>gene on chromosome 22 to form the <it>BCR</it>/<it>ABL1 </it>fusion gene. At diagnosis, in 5-10% of CML patients the Ph chromosome is derived from variant translocations other than the standard t(9;22).</p> <p>Results</p> <p>We report a molecular cytogenetic study of 452 consecutive CML patients at diagnosis, that revealed 50 cases identifying three main subgroups: i) cases with variant chromosomal rearrangements other than the classic t(9;22)(q34;q11) (9.5%); ii) cases with cryptic insertions of <it>ABL1 </it>into <it>BCR</it>, or vice versa (1.3%); iii) cases bearing additional chromosomal rearrangements concomitant to the t(9;22) (1.1%). For each cytogenetic group, the mechanism at the basis of the rearrangement is discussed.</p> <p>All breakpoints on other chromosomes involved in variant t(9;22) and in additional rearrangements have been characterized for the first time by Fluorescence In Situ Hybridization (FISH) experiments and bioinformatic analyses. This study revealed a high content of <it>Alu </it>repeats, genes density, GC frequency, and miRNAs in the great majority of the analyzed breakpoints.</p> <p>Conclusions</p> <p>Taken together with literature data about CML with variant t(9;22), our findings identified several new cytogenetic breakpoints as hotspots for recombination, demonstrating that the involvement of chromosomes other than 9 and 22 is not a random event but could depend on specific genomic features. The presence of several genes and/or miRNAs at the identified breakpoints suggests their potential involvement in the CML pathogenesis.</p
    • …
    corecore