EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is a recessive disorder typified by bone marrow failure and predisposition to hematological malignancies. SDS is predominantly caused by deficiency of the allosteric regulator Shwachman-Bodian-Diamond syndrome that cooperates with elongation factor-like GTPase 1 (EFL1) to catalyze release of the ribosome antiassociation factor eIF6 and activate translation. Here, we report biallelic mutations in EFL1 in 3 unrelated individuals with clinical features of SDS. Cellular defects in these individuals include impaired ribosomal subunit joining and attenuated global protein translation as a consequence of defective eIF6 eviction. In mice, Efl1 deficiency recapitulates key aspects of the SDS phenotype. By identifying biallelic EFL1 mutations in SDS, we define this leukemia predisposition disorder as a ribosomopathy that is caused by corruption of a fundamental, conserved mechanism, which licenses entry of the large ribosomal subunit into translation.Medical Research Council, Bloodwise, Wellcome Trust, Ted’s Gang, The Connor Wright Shwachman Diamond Projec

Admission précoce en réanimation chez des patients atteints de leucémie aiguë myéloblastique

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Hydroxyurée avant chimiothérapie intensive chez des patients atteints de leucémies aiguës myéloïdes hyperleucocytaires

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Endothelial cells: major players in acute myeloid leukaemia

International audienc

Acute Kidney Injury in Patients with Newly Diagnosed High-Grade Hematological Malignancies: Impact on Remission and Survival

<div><h3>Background</h3><p>Optimal chemotherapy with minimal toxicity is the main determinant of complete remission in patients with newly diagnosed hematological malignancies. Acute organ dysfunctions may impair the patient’s ability to receive optimal chemotherapy.</p> <h3>Design and Methods</h3><p>To compare 6-month complete remission rates in patients with and without acute kidney injury (AKI), we collected prospective data on 200 patients with newly diagnosed high-grade malignancies (non-Hodgkin lymphoma, 53.5%; acute myeloid leukemia, 29%; acute lymphoblastic leukemia, 11.5%; and Hodgkin disease, 6%).</p> <h3>Results</h3><p>According to RIFLE criteria, 137 (68.5%) patients had AKI. Five causes of AKI accounted for 91.4% of cases: hypoperfusion, tumor lysis syndrome, tubular necrosis, nephrotoxic agents, and hemophagocytic lymphohistiocytosis. Half of the AKI patients received renal replacement therapy and 14.6% received suboptimal chemotherapy. AKI was associated with a lower 6-month complete remission rate (39.4% vs. 68.3%, <em>P</em><0.01) and a higher mortality rate (47.4% vs. 30.2%, <em>P</em><0.01) than patients without AKI. By multivariate analysis, independent determinants of 6-month complete remission were older age, poor performance status, number of organ dysfunctions, and AKI.</p> <h3>Conclusion</h3><p>AKI is common in patients with newly diagnosed high-grade malignancies and is associated with lower complete remission rates and higher mortality.</p> </div

IKZF1 alterations predict poor prognosis in adult and pediatric T-ALL

International audienceNo abstract availabl

Outcome data.

<p>IQR, interquartile range; AKI, acute kidney injury.</p

6-month outcome probabilities in patients with newly diagnosed hematological malignancies.

<p>A three-state model was used: alive with hematological malignancy, alive in complete remission, and dead. All patients start in state alive with hematological malignancy. The black line represents the overall survival and the dashed line current survival free of malignancy, defined as the probability of being alive and in complete remission. Results are presented for the whole cohort and stratified according to the presence of AKI at day 1. AKI, acute kidney injury; ICU, intensive care unit.</p