The iron fist: malaria and hepcidin.

distinct clusters (#3 and #11) highly enriched for SF mutations and RAEB/AML-LBC phenotypes with significantly lower bone marrow blast counts, together with known clusters characterized by the presence of t(8;21), inv(16), t(15;17), and CEBPA mutations. 9,10 Interestingly, whole exome sequencing of 14 cases with SF mutations within the 2 clusters revealed mutations in 3 genes implicated in RNA splicing. Among the 2 clusters, #11 was characterized by an erythroid signature with higher erythroblast percentages and differentially expressed or hypomethylated genes involved in erythroid development, whereas cluster #3 was significantly enriched for NRAS/KRAS mutations and poor overall survivals compared with other patients. Although the conclusions need to be validated further in independent studies with more comprehensive detection of SF mutations, not just hot-spot mutations, the present study points to an intriguing possibility that SF mutations could override the conventional separation between AML and MDS and help to define novel biological subtypes of myeloid malignancies for better understanding and management of AML/ MDS. However, the biological basis for the SF-mutated AML is still unclear, as is the reason why the 2 SF-mutated clusters are identified only through combined GEP and DMP analysis. Finally, and more importantly, the impact of the SF-mutated AML or the novel clusters identified through GEP/DMP profiling on the choice of therapies and patients' outcomes should be clarified before these subtypes are found to be relevant to clinical practice. Conflict-of-interest disclosure: The author declares no competing financial interests. n REFERENCES 1. Taskesen E, Havermans M, van Lom K, et al. Two splice-factor mutant leukemia subgroups uncovered at the boundaries of MDS and AML using combined gene expression and DNA-methylation profiling. and biological implications of driver mutations in myelodysplastic syndromes. methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. In this issue of Blood, Atkinson and colleagues document dynamic fluctuations in plasma concentrations of hepcidin, the master regulator of iron homeostasis, in African children during malaria transmission season and further show that low hepcidin levels and iron deficiency are more prevalent at the end of the malaria season, implying that iron therapy may be most beneficial at this time. 1 O ur understanding of iron homeostasis in humans has made huge strides in the last decade, and Atkinson and colleagues have now brought the new knowledge to bear on the troubling clinical problem of iron deficiency in malaria. 1 Iron deficiency with or without anemia commonly accompanies malaria, especially …