Efficacy of Chemotherapy in Acute Leukemia Patients Resistant to Previous Standard Treatment According to the Series Measurement of WT1 Gene Expression

Aim. To estimate the efficacy of chemotherapy in acute leukemia patients resistant to previous standard treatment according to the series measurement of WT1 expression. Materials & Methods. The series measurement of WT1 expression formed the basis of the efficacy estimation of induction chemotherapy in 31 patients (15 men and 16 women aged from 3 months to 68 years; the median age was 28 years) with prognostically unfavourable variants of acute myeloid (AML) and lymphoblastic leukemia (ALL) (23 AML and 8 ALL patients). The WT1 gene expression was measured at baseline and 2–3 weeks after the treatment by the quantitative real-time PCR. The threshold level for detection was 250 copies of WT1/104 copies of ABL. The cytogenetic profile of leukemia cells was assessed by standard cytogenetics and FISH. Results. The baseline expression level of WT1 varied from 305 to 58,569 copies/104 copies of ABL. The expected reduction of WT1 expression after the first induction chemotherapy treatment was reported in 22/23 (96 %) AML patients and in 6/8 (75 %) ALL patients. According to our results WT1 expression reached the threshold in 13/31 (42 %) patients, including 9 AML patients and 4 ALL patients. After 11/31 (35 %) patients received the second course of treatment, WT1 expression level became normal in 8 cases (5 ALL and 3 AML patients). Despite high dose chemotherapy, HSCT and such agents as blinatumomab and gemtuzumab, an unfavourable outcome was observed in 18/31 (58 %) patients including 6 patients with complex karyotype (CK+) and 2 patients with monosomal karyotype (MK+). Once the MK+ and CK+ combination was observed, in another case the MK+ was combined with the prognostically unfavourable inv(3)(q21q26) inversion. Conclusion. Our results show that the molecular monitoring should be included as part of treatment of the prognostically unfavourable acute leukemia. The WT1 gene was shown to be the most appropriate marker. WT1 expression was shown to correlate with the common fusion genes allowing to estimate the blast cell count at the molecular level

Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis

Background & Aims. At present, the allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment option with curative potential in patients with myelofibrosis (MF), especially in intermediate and high risk categories. The aim of the study is to perform a retrospective analysis of allo-HSCT outcomes in MF patients. Materials & Methods. Outcomes of allo-HSCT in 11 intermediate-2 (n = 3) and high (n = 6) risk patients (based on Dynamic International Prognostic Scoring Scale, DIPSSplus) performed in the R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation over the period from 2005 till 2015 were analyzed in the study. Two more patients underwent allo-HSCT in MF blast phase. Two patients received ruxolitinib before allo-HSCT and 1 patient before and after allo-HSCT. Reduced intensity conditioning regimen was used in all cases. Results. Primary engraftment was documented in 8 patients. 72 % of patients achieved complete hematological remission. Molecular remission and myelofibrosis regression were confirmed in 5 patients. 5 of 11 patients were still with remission and followed-up by the date of the paper submission. The overall two-year survival was 46 %. Conclusion. Allo-HSCT is an effective treatment option for MF patients. Further trials are required to evaluate an optimal timing for allo-HSCT in MF patients and efficacy of Janus kinase (JAK) inhibitors as pre- and posttransplant therapy in MF

New Сytogenetic Approaches in Patients with Primary Myelofibrosis

Aim. To evaluate the potential of a new cytogenetic technique in patients with primary myelofibrosis (PMF). Materials and methods. 48-hour blood cell cultures (according to Singh et al., 2013) were used for cytogenetic study in 11 PMF patients (5 female, 6 men, aged 32–60 years; median 48.6 years). GTG-banding and different types of fluorescence in situ hybridization (FISH) techniques were used for identification of chromosomal aberrations. Results. The incidence of abnormal karyotypes in blood cultures was significantly higher than that in standard bone marrow cultures (82 vs 27 %; p < 0.01). The polyploid clones were found in blood cultures of 45 % of patients. Structural chromosomal aberrations were found in chromosomes 6, 1, 3, as well as 16 and 17 (in 2 and 1 patients with each aberration, respectively). In all but one patients these abnormalities in diploid and polyploid metaphases were identical. Partial 1q trisomy resulted from adding of additional (1q21–1q44) material translocated to the short arm of chromosome 5 to the material of 2 normal homologue of chromosome 1. It seems that 1q+, i(17q) and some others chromosomal abnormalities were secondary, whereas 6p21 locus involvement may be a primary defect in PMF. The t(3;6)(q25;p21) translocation described for the first time and confirmed by FISH should be considered a variant of well-known translocation t(1;6). Allo-HSCT in 2 patients with 1q+ was successful, whereas there were problems with engraftment in a female patient with prognostically unfavorable t(3;3)(q21;q26) translocation associated with the EVI1 gene overexpression. Conclusion. Cytogenetic examinations in blood cultures provide important additional information about PMF patients

Quantum Optical Phenomena in Nuclear Resonant Scattering

With the advent of high-brilliance, accelerator-driven light sources such as modern synchrotron radiation sources or x-ray lasers, it has become possible to extend quantum optical concepts into the x-ray regime. Owing to the availability of single photon x-ray detectors with quantum efficiencies close to unity and photon-number resolving capabilities, fundamental phenomena of quantum optics can now also be studied at Angstrom wavelengths. A key role in the emerging field of x-ray quantum optics is taken by the nuclear resonances of Mössbauer isotopes. Their narrow resonance bandwidth facilitates high-precision studies of fundamental aspects of the light-matter interaction. A very accurate tuning of this interaction is possible via a controlled placement of Mössbauer nuclei in planar thin-film waveguides that act as cavities for x-rays. A decisive aspect in contrast to conventional forward scattering is that the cavity geometry facilitates the excitation of cooperative radiative eigenstates of the embedded nuclei. The multiple interaction of real and virtual photons with a nuclear ensemble in a cavity leads to a strong superradiant enhancement of the resonant emission and a strong radiative level shift, known as collective Lamb shift. Meanwhile, thin-film x-ray cavities and multilayers have evolved into an enabling technology for nuclear quantum optics. The radiative coupling of such ensembles in the cavity field can be employed to generate atomic coherences between different nuclear levels, resulting in phenomena including electromagnetically induced transparency, spontaneously generated coherences, Fano resonances and others. Enhancing the interaction strength between nuclei in photonic structures like superlattices and coupled cavities facilitates to reach the regime of collective strong coupling of light and matter where phenomena like normal mode splitting and Rabi oscillations appear. These developments establish Mössbauer nuclei as a promising platform to study quantum optical effects at x-ray energies. In turn, these effects bear potential to advance the instrumentation and applications of Mössbauer science as a whole

Self-similarity in ultrafast nonlinear optics

International audienceRecent developments in nonlinear optics have led to the discovery of a new class of ultrashort pulse, the `optical similariton'. Optical similaritons arise when the interaction of nonlinearity, dispersion and gain in a high-power fibre amplifier causes the shape of an arbitrary input pulse to converge asymptotically to a pulse whose shape is self-similar. In comparison with optical solitons, which rely on a delicate balance of nonlinearity and anomalous dispersion and which can become unstable with increasing intensity, similaritons are more robust at high pulse powers. The simplicity and widespread availability of the components needed to build a self-similar amplifier capable of producing optical similaritons provides a convenient experimental platform to explore the fundamental nature of dynamical self-similarity. Here, we provide an overview of self-similar pulse propagation and scaling in optical fibre amplifiers, and their use in the development of high-power ultrafast optical sources, pulse synthesis and all-optical pulse regeneration