Graphical abstract

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Highlights

     * Platelet transcriptome yields progressive markers across MPN
       subtypes
     * Lasso-penalized multinomial regression model predicts advanced MPNs
     * Impaired protein homeostasis and an integrated stress response
       feature in MPN progression
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   Shen et al. leverage two independent MPN patient cohorts to identify
   progressive platelet transcriptomic markers, which also enable an
   externally validated prediction for advanced MPNs. The platelet RNA-seq
   data identify impaired protein homeostasis in MPN progression and offer
   potential targets of therapy.

Introduction

   The classic Philadelphia chromosome-negative (Ph^-) MPNs,[43]5, [44]6,
   [45]7, [46]8 are clonal disorders of the bone marrow that comprise
   three clinical phenotypes– essential thrombocythemia (ET), polycythemia
   vera (PV), and myelofibrosis (MF). These myeloid neoplasms are defined
   by a combination of morphologic, clinical, laboratory, and
   cytogenetic/molecular genetic features. The existing genetic
   landscape[47]9, [48]10, [49]11 of MPNs primarily involves mutations in
   three driver genes that lead to constitutive JAK-STAT signaling (JAK2,
   CALR, MPL). Several additional non-driver mutations (see
   references[50]9, [51]10, [52]11, [53]12, [54]13, [55]14, [56]15 for