Ineffective haematopoiesis in bone marrow and peripheral cytopenias are features of bone marrow failure and related syndromes. These diseases can progress to myelodysplastic syndrome, acute myeloid leukaemia, and other malignancies. Acute myeloid leukaemia is a heterogeneous complex malignancy characterized by proliferating myeloblasts in the bone marrow and a diverse range of recurrent molecular aberrations that occur in many different combinations. More specifically, the authors explore the McDonough strain of feline sarcoma virus-related tyrosine kinase 3 receptor mutations present in about 30-35% of acute myeloid leukaemia patients. The way in which the Wnt signalling pathway plays an important role in normal haematopoiesis and its deregulation associated with acute myeloid leukaemia is also discussed. This compilation also explores the importance of residual leukemic cells in disease relapse prognosis, as the new definition of the European LeukemiaNet for complete remission includes minimal or measurable residual disease negativity. Mutations detected in patients with clonal haematopoiesis are addressed, including those which most commonly affect DNMT3A, ASXL1, TET2, JAK2, SF3B1, SRSF2, and TP53 genes that had previously been identified as drivers in various myeloid neoplasms. The authors provide an overview of the roles of extracellular vesicles in multiple myeloma, their capacity as emerging biomarkers, and implications for liquid biopsy for detection and monitoring. The penultimate study focuses on toll-like receptors, which play an essential role in the recognition of invading pathogens via specific microbial molecular motifs, forming a bridge between the innate and adaptive immune responses. In conclusion, this compilation explores PROTACs, proteolysis targeting chimeras, which mediate the degradation of proteins of interest by hijacking the activity of E3-ubiquitin ligases for POI polyubiquitination and subsequent degradation by proteasome.
Preface; Inherited Bone Marrow Failure and Genetic Predisposition to Myelodysplastic Syndrome and Acute Myeloid Leukemia; The Phosphatidylinositol 3-Kinase (PI3K) Pathway in Acute Myeloid Leukemia and Inhibition of Mechanistic Target of Rapamycin (mTOR) as a Therapeutic Target; Targeting Oncogenic Signaling in Mutant FLT3 Acute Myeloid Leukemia by FLT3 Tyrosine Kinase Inhibitors; Aberrant Wnt / β-Catenin Signaling Pathway in Acute Myeloid Leukemia; Minimal or Measurable Residual Disease Detection in Acute Myeloid Leukemia; Clonal Hematopoiesis as a Precursor of Myeloid Cancers; Understanding the Role of Extracellular Vesicles in Multiple Myeloma; Toll-Like Receptors Signaling Pathways in Hematologic Malignancies; Targeted Protein Degradation Using Proteolysis Targeting Chimeras (PROTACs) in Hematologic Malignancies; Index.
