Diagnostics and treatment challenges of Ph-like acute lymphoblastic leukemia: a description of 3 clinical cases

B-cell acute lymphoblastic leukemia (B-ALL) is a diverse group of malignant blood disorders both with regard to the biological properties of the tumor and to therapeutic approaches. Immunophenotyping, molecular genetic techniques, whole-genome sequencing characterize B-ALL as a very diverse group for sensitivity to chemotherapy and prognosis. We present three clinical cases of patients with B-ALL and expected good response to standard therapy, in whom standard protocol treatment failured: refractoriness, persistence of minimal residual disease (MRD), and progression (MRD increase). The remission in these patients was achieved after chemotherapy change to immunological targeted therapy. Nowadays a unified therapeutic approach to all primary patients of the B-ALL is considered generally outdated. Great efforts are carrying out to develop molecular genetic classifications. The molecular dissection of subtypes of B-ALL goes on, and new protocols for selective treatment with targeting are clearly outlined for each subtype of B-ALL

Subnational climate entrepreneurship: innovative climate action in California and São Paulo

The distinct role of subnational governments such as states and provinces in addressing climate change has been increasingly acknowledged. But while most studies investigate the causes and consequences of particular governments’ actions and networking activities, this article argues that subnational governments can develop climate action as a collective entrepreneurial activity. Addressing many elements explored in this special issue, it focuses on the second question and identifies climate entrepreneurship in two subnational governments—the states of California (USA) and São Paulo (Brazil). Examining internal action, as well as interaction with local authorities, national governments and the international regime, entrepreneurial activities are identified in the invention, diffusion and evaluation of subnational climate policy in each case. The article draws from the recent scholarship on policy innovation, entrepreneurship and climate governance. It contributes to the literature by exploring entrepreneurial subnational government activity in addressing climate change and expanding the understanding of the effects of policy innovation at the subnational level

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III

The energy method of analysis of rubber shells of revolution : translation no. 3

http://deepblue.lib.umich.edu/bitstream/2027.42/3584/5/bab2196.0001.001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/3584/4/bab2196.0001.001.tx

Genetic Lesions in Russian CLL Patients with the Most Common Stereotyped Antigen Receptors

Chronic lymphocytic leukemia (CLL) is one of the most common B-cell malignancies in Western countries. IGHV mutational status is the most important prognostic factor for this disease. CLL is characterized by an extreme narrowing of the IGHV genes repertoire and the existence of subgroups of quasi-identical stereotyped antigenic receptors (SAR). Some of these subgroups have already been identified as independent prognostic factors for CLL. Here, we report the frequencies of TP53, NOTCH1, and SF3B1 gene mutations and chromosomal aberrations assessed by NGS and FISH in 152 CLL patients with the most common SAR in Russia. We noted these lesions to be much more common in patients with certain SAR than average in CLL. The profile of these aberrations differs between the subgroups of SAR, despite the similarity of their structure. For most of these subgroups mutations prevailed in a single gene, except for CLL#5 with all three genes affected by mutations. It should be noted that our data concerning the mutation frequency in some SAR groups differ from that obtained previously, which could be due to the population differences between patient cohorts. The research in this area should be important for better understanding the pathogenesis of CLL and therapy optimization

The repertoire of heavy chain immunoglobulin genes in B‑cell chronic lymphocytic leukemia in Russia and Belarus

Mutation status of the heavy chain variable region genes has long been known as an important factor in long‑term prognosis in B‑cell chronic lymphocytic leukemia (B‑CLL). A more detailed study of the gene sequences of immunoglobulin heavy chain (IgVH) led to the discovery of stereotyped antigen receptors (SAR) — receptors that have the same set of VH‑, D‑ and JH‑genes used. Cells with SARs have been found almost in a quarter of all B‑CLL cases. This phenomenon is not observed in other lymphatic tumors. In our study, we confirmed and extended the basic observations concerning the repertoire of IgVH in B‑CLL. Differences in the B‑CLL IgVH gene repertoirs between Russia, Вelarus and other countries are also analysed and discussed.</p

BRAF and MAP2K1 mutations in hairy cell leukemia and splenic marginal zone B-cell lymphoma

DNA samples from patients with hairy cell leukemia (HCL) and splenic marginal zone B-cell lymphoma (MZBCL) for BRAF and MAP2K1 activating mutations were analyzed. V600E mutation of BRAF was detected in 39 (98 %) of 40 patients with hairy cell leukemia, and no patient with MZBCL. In none of the patients in this study any other activating mutations than V600E in exons 11 and 15 of BRAF gene were revealed. MAP2K1 Q56P mutation characterized by IGHV4-34 expression was detected in 1 (2 %) of 40 patients with HCL. In none of the patients with MZBCL activating mutations in the 2, 3 or 11 exons of MAR2K1 gene have been identified, including those with IGHV4-34 expression