0000000000099274
AUTHOR
Marie-lorraine Chretien
Carfilzomib Weekly Plus Melphalan and Prednisone in Newly Diagnosed Elderly Multiple Myeloma (IFM 2012-03) / 57th Annual Meeting of the American-Society-of-Hematology - Orlando, FL
WOS:000368020103223; International audience; Conference: 57th Annual Meeting of the American-Society-of-Hematology - Orlando, FL - DEC 05-08, 2015
Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells.
The hematopoietic system declines with age. Myeloid-biased differentiation and increased incidence of myeloid malignancies feature aging of hematopoietic stem cells (HSCs), but the mechanisms involved remain uncertain. Here, we report that 4-mo-old mice deleted for transcription intermediary factor 1γ (Tif1γ) in HSCs developed an accelerated aging phenotype. To reinforce this result, we also show that Tif1γ is down-regulated in HSCs during aging in 20-mo-old wild-type mice. We established that Tif1γ controls TGF-β1 receptor (Tgfbr1) turnover. Compared with young HSCs, Tif1γ(-/-) and old HSCs are more sensitive to TGF-β signaling. Importantly, we identified two populations of HSCs specifical…
Assessment of Mobilization Cost for Multiple Myeloma Using 2 Different Mobilization Strategies: High-Dose Cyclophosphamide Versus Plerixafor. on Behalf of IFM
Abstract Background. Peripheral blood stem cell (PBSC) collection prior to high dose chemotherapy for autologous transplantation (ASCT) is a standard of care, and an attractive alternative to the use of bone marrow cells, for transplantation in Multiple Myeloma (MM). The optimal methodology for mobilizing PBSC has yet to be defined, both G-CSF and GM-CSF can be used; although, the stimulatory effect may be more pronounced when given after high dose cyclophosphamide (usually administered at a dose of 1.5 to 6g/m2 IV for one to two days) and use of Plerixafor, a CXCR4 antagonist (Mozobil®). The latter 2 options are preferred, overall, in France. Indeed, it was shown that the most recent combi…
Identification of novel, clonally stable, somatic mutations targeting transcription factors PAX5 and NKX2-3, the epigenetic regulator LRIF1, and BRAF in a case of atypical B-cell chronic lymphocytic leukemia harboring a t(14;18)(q32;q21)
Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) is usually straightforward, involving clinical, immunophenotypic (Matutes score), and (immuno)genetic analyses (to refine patient prognosis for treatment). CLL cases with atypical presentation (e.g., Matutes ≤ 3) are also encountered, and for these diseases, biology and prognostic impact are less clear. Here we report the genomic characterization of a case of atypical B-CLL in a 70-yr-old male patient; B-CLL cells showed a Matutes score of 3, chromosomal translocation t(14;18)(q32;q21) (BCL2/IGH), mutated IGHV, deletion 17p, and mutations in BCL2, NOTCH1 (subclonal), and TP53 (subclonal). Quite strikingly, a novel PAX5 mutation that w…
Generic vancomycin products: Analysis of serum concentrations in patients with acute myeloid leukemia.
Summary Concerns have recently emerged about the quality of generic vancomycin products. Our aim is to analyze serum vancomycin concentrations measured 48 hours after the start of an empirical treatment regimen in patients with acute myeloid leukemia (AML) who received one of the two generic vancomycin products available in France. Patients and methods Seventy-nine AML patients treated with vancomycin during two study periods were included in the study. Our vancomycin dosing regimen was based on the patients’ total body weight adjusted for renal clearance. Results A total of 93 serum vancomycin concentrations were collected: 31 in period 1 and 62 in period 2. In bivariate analysis, the mean…
Rôle de Tif1gamma dans les différenciations granulo-monocytaire et macrophagique
Chronic myelomonocytic leukemia (CMML) is a hematologic stem cell disease whose characteristics correspond to myelodysplastic/myeloproliferative syndroms (MDS/MPS). Hematopoietic conditional deletion of Tif1γ in mice leads to the development of a MDS/MPS, mimiking human CMML, when age is comprised between 6 to 10 months, defining Tif1γ as a tumour suppressor gene. Moreover, peritoneal macrophage population in these mice is decreased despite a monocytosis.The aims of my work were first to characterize in sick mice the myeloid population, and second to study macrophage differentiation. The myeloid population in Tif1γΔ/Δ mice is morphologically immature, with granulocytic and monocytic feature…
Adherence to immunomodulatory drugs in patients with multiple myeloma
Background Immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide; IMID) are widely used in the treatment of multiple myeloma patients. To date, few data are available on IMID adherence in multiple myeloma patients. The aim of our study was to evaluate IMID adherence and to compare two indirect methods to measure IMID adherence in multiple myeloma patients: a specific questionnaire and the medication possession ratio (MPR). Another aim was to explore this specific questionnaire for the assessment of IMID adherence in multiple myeloma patients. Methods All consecutive multiple myeloma patients, with at least two consecutive dispensations of thalidomide, lenalidomide or pomalidomi…
Leukocytosis is associated with poor survival but not with increased risk of thrombosis in essential thrombocythemia: a population-based study of 311 patients
Leukocytosis is associated with poor survival but not with increased risk of thrombosis in essential thrombocythemia: a population-based study of 311 patients
Tif1gamma Is Essential for Macrophage Differentiation
Abstract Abstract 2370 TIF1gamma (or TRIM33) is an ubiquitous nuclear protein that belongs to the transcriptional intermediary factor 1 family. Human and mouse TIF1gamma are closely related to zebrafish moonshine (mon), a gene whose mutations disrupt embryonic and adult hematopoiesis with severe red blood cell aplasia. Targeted deletion of Tif1gamma is embryonic lethal in mice. In zebrafish and human CD34+ cells, TIF1gamma functionally links positive elongation factors such as p-TEFb and FACT to blood specific transcription complexes (e.g. the SCL/TAL1 complex) to regulate elongation of genes by antagonizing Pol II pausing. TIF1gamma also affects the human hematopoietic progenitor cell resp…
Self‐management of immunomodulatory drug treatment in multiple myeloma patients
Objective Immunomodulatory drugs (IMIDs: thalidomide, lenalidomide and pomalidomide) are widely used in patients with multiple myeloma (MM). The aim of our study was to validate a questionnaire to evaluate the self-capacity of MM patients to manage IMID treatment including side effects. Methods We used a method adapted from the recommendations of the European Organisation for Research and Treatment of Cancer (EORTC) to validate a French questionnaire for patients with MM treated with IMIDs. Results The face validity was evaluated in 15 patients and the construct validity in 56 patients. For discriminant validity, two groups were constituted by gender and depending on whether they had a prev…