About this Research Topic
More than 250,000 people throughout the world are diagnosed every year with acute leukemia. Acute leukemia with chromosomal translocations affecting the KMT2A gene (also known as MLL) is a particular aggressive and often chemo-refractory acute leukemia. Currently no targeted therapeutics are available for KMT2A-rearranged (KMT2A-R) leukemia in the clinic. The current treatment protocols, based on chemotherapy and bone marrow transplantation, are highly toxic and most patients either do not respond or relapse due to mechanisms not completely elucidated. Persistence in the bone marrow (BM) of self-renewing leukemic stem cells (LSC), acquisition of secondary mutations, aberrant regulation of cell signaling, cell cycle and DNA damage repair are among the mechanisms likely to contribute to the chemo-refractory phenotype of KMT2A-R-leukemia. Transcriptome aberrancies and circular RNAs are under investigation for their contribution to KMT2A-R leukemia. Recent technological advances in genomics, proteomics, gene editing and development of in vitro and in vivo models are enabling the scientific community to increase our understanding of KMT2A-R leukemia.
In order to translate these advancements into novel pharmacological strategies we need to 1) improve our understanding of the basic molecular mechanisms of chemotherapy resistance and biology of the disease, 2) identify novel therapeutic targets, 3) validate these targets into suitable pre-clinical models and 4) drive the development of novel pharmacological inhibitors or repositioning strategies. The Research Topic aims to boost the elucidation of KMT2A-R leukemia disease mechanisms and to facilitate the development of innovative therapies.
Areas to be covered in this Research Topic may include, but are not limited to:
o Development of novel mouse models of KMT2A-R leukemias
o Development of novel cell based models of KMT2A-R leukemias
o Identification of secondary mutations in KMT2A-R leukemias
o Progress in understanding the epigenetic landscape of KMT2A-R leukemias
o Role of Transcriptome aberrancies to KMT2A-R leukemias
o Novel therapeutic strategies
o Agents that increase sensitivity to standard chemotherapy
o Contributing factors to chemotherapy resistance
Keywords: KMT2A, MLL, leukemia, therapy, epigenetics
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