Definitions, Biology, and Current Therapeutic Landscape of Myelodysplastic/Myeloproliferative Neoplasms

SIMPLE SUMMARY: Myelodysplastic/myeloproliferative (MDS/MPN) neoplasms are blood disorders characterized by abnormal cell growth and development. These disorders encompass various subtypes, including chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, and others. They are caused by genetic changes in different cell components and have distinct clinical features. Current treatment options mostly involve drugs that control the disease, including hypomethylating agents, ruxolitinib, lenalidomide, and venetoclax, but do not offer a cure. However, allogeneic bone marrow transplantation has the potential to cure these disorders. Several factors, such as overall health, spleen enlargement, and genetic alterations, can influence the outcome of transplantation. Future research is crucial to improving treatment approaches and patient outcomes for MDS/MPN neoplasms. This review provides an overview of the diagnosis, biology, and current and upcoming treatments, including bone marrow transplantation, for these complex blood disorders. This review will shed light on the complexities of MDS/MPN neoplasms and will inform future research for improved therapeutic strategies and patient care in the future. ABSTRACT: Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are hematological disorders characterized by both proliferative and dysplastic features. According to the 2022 International Consensus Classification (ICC), MDS/MPN consists of clonal monocytosis of undetermined significance (CMUS), chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), MDS/MPN with SF3B1 mutation (MDS/MPN-T-SF3B1), MDS/MPN with ring sideroblasts and thrombocytosis not otherwise specified (MDS/MPN-RS-T-NOS), and MDS/MPN-NOS. These disorders exhibit a diverse range of genetic alterations involving various transcription factors (e.g., RUNX1), signaling molecules (e.g., NRAS, JAK2), splicing factors (e.g., SF3B, SRSF2), and epigenetic regulators (e.g., TET2, ASXL1, DNMT3A), as well as specific cytogenetic abnormalities (e.g., 8 trisomies, 7 deletions/monosomies). Clinical studies exploring therapeutic options for higher-risk MDS/MPN overlap syndromes mostly involve hypomethylating agents, but other treatments such as lenalidomide and targeted agents such as JAK inhibitors and inhibitors targeting PARP, histone deacetylases, and the Ras pathway are under investigation. While these treatment modalities can provide partial disease control, allogeneic bone marrow transplantation (allo-BMT) is the only potentially curative option for patients. Important prognostic factors correlating with outcomes after allo-BMT include comorbidities, splenomegaly, karyotype alterations, and the bone marrow blasts percentage at the time of transplantation. Future research is imperative to optimizing therapeutic strategies and enhancing patient outcomes in MDS/MPN neoplasms. In this review, we summarize MDS/MPN diagnostic criteria, biology, and current and future treatment options, including bone marrow transplantation.