Calreticulin and JAK2V617F driver mutations induce distinct mitotic defects in myeloproliferative neoplasms

• We have found that main driver mutations in Myeloproliferative Neoplasms (MPNs), namely CARLdel52 and JAK2V617F, disrupt the molecular regulation of mitosis, leading to aberrant chromatin segregation. It is just available at Scientific Reports.
• This disruption potentially plays a pivotal role in the shift from chronic to acute MPN states. Mitotic errors, characterized by chromosome bridges, lagging chromosomes, and micronuclei—often undergoing chromothripsis—are well-known contributors to the heightened aggressiveness observed in solid tumors. Our study proposes that the karyotype aberrations noted at MPN diagnosis, accumulating during blast-phase transformation and linked to decreased survival, result not only from DNA replication and repair defects but also from flawed mitosis, notably attributed to a defective spindle assembly checkpoint.
• We make strides in suggesting a plausible molecular mechanism, thus unveiling novel avenues for both basic and therapeutic research in these diseases.
• This has been possible thanks to our close collaboration with the Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University.