Pathogenesis of myeloid malignancies

Abstract

Myeloid malignancies are heterogenous group of disorders with complex molecular background and pathogenesis. Recent advances in understanding molecular mechanisms underlying malig­nant transformation allowed to rationalize and organize classification of these diseases and also provided molecular markers for more precise stratification of patients to risk groups. Myeloid malignancies originate from the hematopoietic stem and progenitor cells, in which genetic and epigenetic alterations lead to the abnormal gene expression, activation of oncogenes, inactivation of tumor suppressors, aberrant signal transduction and deregulation of transcription factors involved in myelopoiesis. As a functional consequence, the key hematopoietic processes such as self-renewal, proliferation and differentiation are disrupted. This review outlines major factors that control nor­mal differentiation of myeloid precursor cells and mechanisms of their deregulation in malignant cells. The manuscript also reviews the prognostic value of discussed alterations in clinical practice.