Abstract
Myelodysplasia refers to a group of clonal hematopoietic neoplasms characterized by genetic heterogeneity, different clinical behaviors and prognoses. Some of this group of bone marrow failure conditions have known external causes, some are of unknown origin. Within marrow, intracellular, and extracellular elements of the innate immune system are activated and contribute to creation of multiple cytogenetic abnormalities and are central to the mode of hematopoietic cell failure. Basiorka et al. showed that NLRP3 inflammasome activity is essential to the innate immune system's destruction of marrow hematopoietic cells commonly in myelodysplasia. In April 2018 Hao et al. reported that methylene blue inhibits rat NLRP3 inflammasome function. Methylene blue has been in continuous use in humans for over a century. It is associated with an eminently benign side effect profile in human use. If as in rodents, methylene blue also inhibits NLRP3 inflammasome function in human myelodysplasia a trial of adjunctive methylene blue treatment in transfusion dependent, low risk myelodysplasia where marrow inflammation and apoptosis predominates, would be worth trying.HIGHLIGHTS - Cytogenetic abnormalities and innate immune activation are seen in myelodysplasia- The NLRP3 inflammasome is a core element generating marrow failure of myelodysplasia- In April 2018 methylene blue was reported to potently inhibit NLRP3 inflammasome function- Methylene blue has benign side effects and has been in human use for a century- Study of methylene blue treatment of myelodysplasia would be a low-risk intervention
Highlights
Myelodysplasia refers to a group of clonal hematopoietic neoplasms characterized by genetic heterogeneity, different clinical behaviors and prognoses
The clinical picture is variable, encompassing hematopoietic failure syndromes with pancytopenia, hypocellular dysplastic marrow, ineffective hematopoiesis, marrow stem cell macrocytosis, production of aberrant clones, a high marrow cell apoptosis rate, and multiple gross cytogenetic abnormalities [2, 3]
MB is clearly effective at stopping cerebral malaria in a murine model where NLRP3 is known to play a pivotal pathogenic role [29, 30]
Summary
Beginning with Paul Ehrlich in the late 1800’s [17] continuing to today, as of 2018 [18,19,20], MB has been used to treat malaria. Under some circumstances MB circumvents mitochondrial complexes 2 and 3 by accepting an electron from complex 1, delivering it to cytochrome C [20, 25]. Of central importance to MDS, three recent independent studies showed that MB inhibits NLRP3 inflammasome function. Ahn et al showed that MB inhibited LPS stimulated increase in murine NLRP3 function [26]. Lin et al showed that MB inhibited murine cord transection initiated NLRP3 activation [27]. Hao et al showed that MB inhibited NLRP3 assembly and function in streptozocin murine model of diabetic retinopathy [28]
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