New Molecular Targets and Novel Strategies in Drug Development to Prevent Relapse in Acute Leukemia

Dear Colleagues,

Acute leukemia (AL) is a heterogeneous group of hematological malignancies originating from immature progenitors of myeloid or T/B cell lymphoid lineages. Leukemogenesis results from the accumulation of genetic alterations in leukocyte progenitors that prevent their further maturation and cause unlimited proliferation. Initially, malignant cells accumulate within the bone marrow (BM), where they crowd out healthy lymphoid precursors, devastate hematopoietic niches, and impair hematopoiesis. Subsequently, some of the malignant cells leave the BM and enter the extramedullary organs, including the lymph nodes, spleen, liver, mediastinal space, and the central nervous system. Although conventional therapies, such as using high-dose multi-agent protocols (glucocorticoids, genotoxic/cytotoxic drugs) and allogenic hematopoietic stem cell transplantation, are effective in achieving remission in many patients, some groups are resistant to them. The small number of chemoresistant leukemic cells that remain after treatment are the main cause of minimal residual disease and subsequent relapse. Understanding the underlying mechanisms of chemoresistance may reveal new molecular targets and allow for the development of novel pharmacological strategies for overcoming AL relapse. Several mechanisms have been proposed as causes of chemoresistance in AL, including epigenetic alterations, metabolic reprogramming, alterations in signaling pathways, a protective microenvironment in leukemogenic niches in BM, alterations in the regulation of autophagy and apoptosis, and the overexpression of multidrug resistance pumps and proteins, among others. This Topic will focus on the current progress towards overcoming chemoresistance in AL by identifying additional molecular and cellular targets and through the application of non-conventional drugs, either alone or in combination with conventional antileukemic agents. Both review and original articles are welcome, as are pre-clinical, translational and clinical studies.

Prof. Dr. Oxana Dobrovinskaya
Dr. Ivan Delgado-Enciso
Topic Editors