Scientists have traditionally studied complex biologic systems by reducing them to simple building blocks. Genome sequencing, high-throughput screening, and proteomics have, however, generated large datasets, revealing a high level of complexity in components and interactions. Systems biology embraces this complexity with a combination of mathematical, engineering, and computational tools for c...

Hematopoiesis is defined as the formation of all types of blood cells from hematopoietic stem cells (HSCs) (Orkin and Zon, 2008). This complex process involves the coordination of intrinsic master blood transcriptional regulators and signaling molecules from the surrounding tissues (Huang and Zon, 2008). Understanding the molecular and cellular mechanisms that drive normal hematopoiesis and hem...

Vitamin D is a steroid hormone with a broad range of biological effects ranging from the classical role as a mediator of calcium and phosphate balance to cellular differentiation and immune modulation. These effects impact normal and dysfunctional hematopoietic and immune function, which may allow an avenue for improved treatment and support of patients suffering from hematologic disorders. In ...

Myelodysplastic syndrome is a closely related group of acquired bone marrow disorders characterized by ineffective and dysplastic hematopoiesis. These clonal disorders frequently progress to acute leukemia. Acute myelomonocytic leukemia with eosinophilia is characterized by an increase in abnormal eosinophils in the bone marrow, relatively good clinical course and inv (16) chromosomal abnormali...

Large granular lymphocytic (LGL) leukemia and myelodysplastic syndromes (MDSs) both typically present with unexplained cytopenias, yet these diseases are pathobiologically distinct and associated with substantial differences in prognosis and therapy. LGL leukemias, including both T-cell LGL leukemia and chronic lymphoproliferative disorder of natural killer (NK) cells, are clonal lymphoid disor...

The clear connection between ribosome biogenesis dysfunction and specific hematopoiesis-related disorders prompted us to examine the role of critical lineage-specific transcription factors in the transcriptional regulation of ribosomal protein (RP) genes during terminal erythroid differentiation. By applying EMSA and ChIP methodologies in mouse erythroleukemia cells we show that GATA1 and PU.1 ...

Myelodysplastic syndrome (MDS) comprises a heterogeneous group of often fatal hematopoietic stem cell disorders for which neither curative nor standard treatment exists. The complex karyotypes and multistep nature of MDS have severely restricted the identification of causative genetic mutations and thus limited insight into new and more effective therapies. Here we describe a zebrafish mutant c...