Emerging translational science discoveries, clonal approaches, and treatment trends in chronic myeloproliferative neoplasms

Abstract

The 60th American Society of Hematology (ASH) held in San Diego in December 2018 was followed by the 13th Post‐ASH chronic myeloproliferative neoplasms (MPNs) workshop on December 4 and 5, 2018. This closed annual workshop, first introduced in 2006 by Goldman and Mughal, was organized in collaboration with Alpine Oncology Foundation and allowed experts in preclinical and clinical research in the chronic MPNs to discuss the current scenario, including relevant presentations at ASH, and address pivotal open questions that impact translational research and clinical management. This review is based on the presentations and deliberations at this workshop, and rather than provide a resume of the proceedings, we have selected some of the important translational science and treatment issues that require clarity. We discuss the experimental and observational evidence to support the intimate interaction between aging, inflammation, and clonal evolution of MPNs, the clinical impact of the unfolding mutational landscape on the emerging targets and treatment of MPNs, new methods to detect clonal heterogeneity, the challenges in managing childhood and adolescent MPN, and reflect on the treatment of systemic mastocytosis (SM) following the licensing of midostaurin.

Platelet transcriptome identifies progressive markers and potential therapeutic targets in chronic myeloproliferative neoplasms

“…Each subtype showed both overlapping and progressively divergent transcriptional pathways, suggesting both a shared signature across all MPN, and unique biological trajectories. Pathway-enrichment analyses confirmed the existence of a shared inflammatory milieu 37,[77][78][79][80][81][82] among MPN. We also confirmed that the JAK1/ JAK2 inhibitor ruxolitinib was associated with inhibition of inflammatory as well as interferon-mediated signaling pathways.…”

Platelet transcriptome yields progressive markers in chronic myeloproliferative neoplasms and identifies putative targets of therapy

“…Each subtype showed both overlapping and progressively divergent transcriptional pathways, suggesting both a shared signature across all MPN, and unique biological trajectories. Pathway-enrichment analyses confirmed the existence of a shared inflammatory milieu (Barbui et al, 2011;Geyer et al, 2015;Hasselbalch and Bjorn, 2015;Koschmieder and Chatain, 2020;Marin Oyarzún and Heller, 2019;Mughal et al, 2019;Skov et al, 2011) among MPN. We also confirmed that the JAK1/JAK2 inhibitor ruxolitinib was associated with inhibition of inflammatory as well as interferon-mediated signaling pathways.…”

Interrogating the molecular genetics of chronic myeloproliferative malignancies for personalized management in 2021

“…However, this has inherent limitations with regard to its lower limit of detection and quantification of BCR-ABL1 transcripts, problems which became important as TKI that were more powerful, compared to imatinib, were developed. 9 This, in turn, affected the definition and identification of deep molecular response (DMR), defined as a greater than 4 (MR4), 4.5 (MR4.5) or 5 (MR5) log reduction in BCR-ABL1 transcripts on the International Scale, below the standardized baseline ( Figure 2). DMR is now recognized to be of considerable clinical importance to prospectively identify Ferrata Storti Foundation patients likely to remain in remission after discontinuing TKI therapy.…”