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Platelets decline during Vaso‐occlusive crisis as a predictor of acute chest syndrome in sickle cell disease

Cell Leukemia/Lymphoma, an extremely rare stem cell disorder characterized by very poor prognosis and association of myeloproliferative neoplasm with T/B-cell lymphoma. Notably, this fusion causes constitutive activation of the FGFR1 kinase and, therefore, it is potentially targetable using drugs such as ponatinib [6]. Indeed, in vitro treatment of patient’s cells with nanomolar concentration of ponatinib caused a potent and specific growth inhibition (Supporting Information Fig. 2). A total of three NPM1 insertions were reported by both standard techniques and RNA-Seq; FLT3-ITD was detected in six samples by RNA-Seq and in four by standard PCR-based techniques (not tested in the remaining two). Although the numbers are too limited to drive definitive conclusions, this suggests comparable sensitivity of standard techniques and RNA-Seq in detecting these variants (Table I). A total of 23 SNV were also identified by RNA-Seq with a median of one variant per patient (range 0–4). Globally, 22/23 SNV have been confirmed by Sanger sequencing, suggesting that the accuracy of our pipeline for SNV detection is 96%. Of the 22 confirmed SNV, 10 were new and 12 were known variants (Table I). Taken globally, these data suggest that a single RNA-Seq analysis performed at diagnosis in AML patients, even in absence of a matched control sample, allows to quickly detect a large number of abnormalities that are not detected using standard clinical tests. This analysis will allow to achieve a better prognostic assessment and to identify potentially new treatment options, such as ponatinib for the patient carrying the ZMYM2-FGFR1 translocation. This is of paramount importance, as the list of clinically available selective inhibitors keeps growing at very fast pace and the discovery of new driver variants may lead to the development of novel targeted therapies (Supporting Information Table I).