Introduction to a review series on molecular mechanisms of hematologic malignancies

Mutations that drive hematologic malignancies can act through a variety of mechanisms, including alterations in transcription, pre-mRNA splicing, RNA metabolism, DNA methylation, and chromatin architecture. While premalignant states may be characterized by a single mutation, such as DNMT3A mutations in clonal hematopoiesis leading to altered DNA methylation, progression to fulminant leukemia requires additional events that introduce alterations in these other mechanisms. It is therefore essential to understand how changes in the pathways that govern the regulation of gene expression.

In this series, experts in the field highlight the impact of chromosomal alterations and genetic mutations on the regulation of gene expression through diverse mechanisms. The series includes the following review articles:

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  Sisi Chen, Salima Benbarche, and Omar Abdel-Wahab, “Splicing factor mutations in hematologic malignancies”

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  Hsuan-Ting Huang and Maria E. Figueroa, “Epigenetic deregulation in myeloid malignancies”

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  Justin C. Wheat and Ulrich Steidl, “Gene expression at a single-molecule level: implications for myelodysplastic syndromes and acute myeloid leukemia”

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  Ying Qing, Rui Su, and Jianjun Chen, “RNA modifications in hematopoietic malignancies: a new research frontier”

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  Johann-Christoph Jann and Zuzana Tothova, “Cohesin mutations in myeloid malignancies”

There has been great progress in the development of targeted agents, but to reach our goal of curing all patients, we need to gain deeper understanding of the consequences of genetic alterations on gene regulatory pathways. To this end, these reviews not only summarize our current understanding of these pathways that contribute to myeloid malignancies, but also discuss new therapeutic avenues, such as PARP inhibitors in cohesin mutant AML and splicing modulators in MDS. We hope that this review series stimulates further groundbreaking basic and clinical advances in hematologic malignancies.