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Purpose: ABL kinase domain mutations have been implicated in the resistance to the BCR-ABL inhibitor imatinib mesylate of Philadelphia-positive (Ph+) leukemia patients. Experimental Design: Using denaturing high-performance liquid chromatography and sequencing, we screened for ABL kinase domain mutations in 370 Ph+ patients with evidence of hematologic or cytogenetic resistance to imatinib. Results: Mutations were found in 127 of 297 (43%) evaluable patients. Mutations were found in 27% of chronic-phase patients (14% treated with imatinib frontline; 31% treated with imatinib post-IFN failure), 52% of accelerated-phase patients, 75% of myeloid blast crisis patients, and 83% of lymphoid blast crisis/Ph+ acute lymphoblastic leukemia (ALL) patients. Mutations were associated in 30% of patients with primary resistance (44% hematologic and 28% cytogenetic) and in 57% of patients with acquired resistance (23% patients who lost cytogenetic response; 55% patients who lost hematologic response; and 87% patients who progressed to accelerated phase/blast crisis). P-loop and T315I mutations were particularly frequent in advanced-phase chronic myeloid leukemia and Ph+ ALL patients, and often accompanied progression from chronic phase to accelerated phase/blast crisis. Conclusions: We conclude that (a) amino acid substitutions at seven residues (M244V, G250E, Y253F/H, E255K/V, T315I, M351T, and F359V) account for 85% of all resistance-associated mutations; (b) the search for mutations is important both in case of imatinib failure and in case of loss of response at the hematologic or cytogenetic level; (c) advanced-phase chronic myeloid leukemia and Ph+ ALL patients have a higher likelihood of developing imatinib-resistant mutations; and (d) the presence of either P-loop or T315I mutations in imatinib-treated patients should warn the clinician to reconsider the therapeutic strategy.

In vitro differentiating agents causing little bone marrow aplasia have been proposed as a specific therapy of myelodysplastic syndromes with excess of blasts. A critical review of the published data is presented. The preliminary results of a cooperative protocol using very low dosage of cytosine arabinoside (3mg/m2/twice daily) with or without androgens are given.

We provide a dataset of 3D coordinate time series of 37 continuous GNSS stations installed for stability monitoring purposes on onshore and offshore industrial settlements along a NW-SE-oriented and ~100-km-wide belt encompassing the eastern Italian coast and the Adriatic Sea. The dataset results from the analysis performed by using different geodetic software (Bernese, GAMIT/GLOBK and GIPSY) and consists of six raw position time series solutions, referred to IGb08 and IGS14 reference frames. Time series analyses and comparisons evidence that the different solutions are consistent between them, despite the use of different software, models, strategy processing and frame realizations. We observe that the offshore stations are subject to significant seasonal oscillations probably due to seasonal environmental loads, seasonal temperature-induced platform deformation and hydrostatic pressure variations. Many stations are characterized by non-linear time series, suggesting a complex interplay between regional (long-term tectonic stress) and local sources of deformation (e.g. reservoirs depletion, sediment compaction). Computed raw time series, logs files, phasor diagrams and time series comparison plots are distributed via PANGAEA (https://www.pangaea.de)., Measurement(s) ground deformation process Technology Type(s) GPS navigation system Factor Type(s) GNSS station • temporal interval Sample Characteristic - Location Adriatic Sea Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.13034372