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The most common diagnosis for pediatric thrombocytopenia is immune thrombocytopenia. Nevertheless, in atypical cases, the hypothesis of an inherited thrombocytopenia has to be investigated. We report a series of cases of a newly described entity, genetic thrombocytopenia with mutation in the ankyrine 26 gene, diagnosed from the exploration of five pediatric cases of thrombocytopenia. This entity is characterized by a moderate thrombocytopenia with normal mean platelet volume, and poorly bleeding. Its transmission is autosomal dominant. Final diagnosis is made by sequencing of a short DNA region of ANKRD26 gene. This pathology can be considered as an hematological malignancy predisposition syndrome.We report the first cohort of pediatric patients diagnosed with thrombocytopenia with mutation in the ankyrine 26. The aim is to underline the specificities of this entity in children and bring it to the knowledge of pediatricians who may be in first place to manage these patients.• Genetic thrombocytopenia with mutation in the ankyrine 26 gene is a recently described entity, which seems to be considered as a predisposition for hematologic malignancies. • The first cohort has been reported in 2011, by Noris et al., in 78 Italian adult patients. What is New: • We describe clinical and biological features of the first pediatric cohort diagnosed with genetic thrombocytopenia with mutation in the ankyrine 26 gene. • It seemed important to consider the pediatric specificities of this entity to enable pediatricians to investigate, diagnose, and manage pediatric patients and their families.

Constitutional dominant loss-of-function mutations in the SPRED1 gene cause a rare phenotype referred as neurofibromatosis type 1 (NF1)-like syndrome or Legius syndrome, consisted of multiple café-au-lait macules, axillary freckling, learning disabilities and macrocephaly. SPRED1 is a negative regulator of the RAS MAPK pathway and can interact with neurofibromin, the NF1 gene product. Individuals with NF1 have a higher risk of haematological malignancies. SPRED1 is highly expressed in haematopoietic cells and negatively regulates haematopoiesis. SPRED1 seemed to be a good candidate for leukaemia predisposition or transformation. We performed SPRED1 mutation screening and expression status in 230 paediatric lymphoblastic and acute myeloblastic leukaemias (AMLs). We found a loss-of-function frameshift SPRED1 mutation in a patient with Legius syndrome. In this patient, the leukaemia blasts karyotype showed a SPRED1 loss of heterozygosity, confirming SPRED1 as a tumour suppressor. Our observation confirmed that acute leukaemias are rare complications of the Legius syndrome. Moreover, SPRED1 was significantly decreased at RNA and protein levels in the majority of AMLs at diagnosis compared with normal or paired complete remission bone marrows. SPRED1 decreased expression correlated with genetic features of AML. Our study reveals a new mechanism which contributes to deregulate RAS MAPK pathway in the vast majority of paediatric AMLs.

Extensive mutational status of genes and clinical outcome in pediatric acute myeloid leukemia

We describe here the large-scale ex vivo production of mature human red blood cells (RBCs) from hematopoietic stem cells of diverse origins. By mimicking the marrow microenvironment through the application of cytokines and coculture on stromal cells, we coupled substantial amplification of CD34(+) stem cells (up to 1.95 x 10(6)-fold) with 100% terminal differentiation into fully mature, functional RBCs. These cells survived in nonobese diabetic/severe combined immunodeficient mice, as do native RBCs. Our system for producing 'cultured RBCs' lends itself to a fundamental analysis of erythropoiesis and provides a simple in vitro model for studying important human viral or parasitic infections that target erythroid cells. Further development of large-scale production of cultured RBCs will have implications for gene therapy, blood transfusion and tropical medicine.

International audience; Background : The purpose of this study was to describe the natural history of severe congenital neutropenia (SCN) in 14 patients with G6PC3 mutations and enrolled in the French SCN registry.Methods : Among 605 patients included in the French SCN registry, we identified 8 pedigrees that included 14 patients with autosomal recessive G6PC3 mutations.Results : Median age at the last visit was 22.4 years. All patients had developed various comordibities, including prominent veins (n = 12), cardiac malformations (n = 12), intellectual disability (n = 7), and myopathic syndrome with recurrent painful cramps (n = 1). Three patients developed Crohn’s disease, and five had chronic diarrhea with steatorrhea. Neutropenia was profound ( A /p.Trp83*) was detected in one pedigree.Conclusions : Severe congenital neutropenia with autosomal recessive G6PC3 mutations is associated with considerable clinical heterogeneity. This series includes the first described case of malignancy in this neutropenia.

NUP214-ABL1 amplification in t(5;14)/HOX11L2-positive ALL present with several forms and may have a prognostic significance