A review on the functional characteristics of the c-Myeloproliferative Leukaemia (c-MPL) gene and its isoforms

The c-MPL-TPO axis regulates hematopoiesis by activating various signalling cascades, including JAK/STAT, MAPK/ERK, and PIK3/AKT. Here, we have summarized how TPO is regulated by c-MPL and, how mutations in the c-MPL regulate hematopoiesis. We also focus on its non-hematological regulatory role in diseases like Unstable Angina and pathways like DNA damage repair, skeletal homeostasis, & apoptotic regulation of neurons/HSCs at the embryonic state. We discuss the therapeutic efficiency of c-MPL and, its potential to be developed as a bio-marker for detecting metastasis and development of chemo-resistance in various cancers, justifying the multifaceted nature of c-MPL. We have also highlighted the importance of c-MPL isoforms and their stoichiometry in controlling the HSC quiescent and proliferative state. The regulation of the ratio of different isoforms through gene-therapy can open future therapeutic avenues. A systematic understanding of c-MPL-isoforms would undoubtedly take one step closer to facilitating c-MPL from basic-research towards translational medicine.